Pain management in cardiac sx

Pain management in cardiac Sx
Dr. E THANIGAI ARASU

Learning objectives
• Understanding pain and its dynamics
• Importance of pain alleviation
• Assessment of pain
• Approach to different types of analgesia
• Literature review

What is pain?
• “An unpleasant sensory and emotional experience associated with,
or resembling that associated with, actual or potential tissue
damage,”
• and is expanded upon by the addition of key Notes.
• Pain is always a personal experience that is influenced to varying
degrees by biological, psychological, and social factors.
• A person’s report of an experience as pain should be respected.
• Although pain usually serves an adaptive role, it may have adverse
effects on function and social and psychological well-being.
• Verbal description is only one of several behaviors to express pain;
inability to communicate does not negate the possibility that a
human or a nonhuman animal experiences pain.

Source of pain in CS
• Sternotomy/thoracotomy
• Pericardiotomy
• Intra op tissue retraction and dissection
• Leg vein harvesting/IMA
• Vascular cannulation sites
• Chest tube.
• Post op: sternal retraction → posterior rib # → brachial plexus injury
→ unexplained non incisional pain. = bone scan

Contd..
• Persistent post op pain: multifactorial
• Tissue destruction, intercostal nerve trauma, scar formation, rib#,
sternal infection, stainless steel wire sutures, costo-chondral
separation.
• Often localized to arms, shoulder or legs.
• brachial plexus neuropathy- rib #, IMA, suboptimal positioning.
• Post op neuralgia of saphenous nerve

Why do we treat pain?
Basic human right.
• ↓ pain and suffering
• ↓complications ( MI, PPC, ileus, stress hormones, DVT, infection,
psychological)
• ↓ likelihood of chronic pain development
• ↑improved patient satisfaction (TJC – standards of Essential
Elements)
• ↑speed of recovery → ↓ LOH
• ↑ QOL.

Contd..,
Clinical benefits:
• Hemodynamic stability
• Metabolic stability
• Immunologic stability
• Hemostatic stability
• Stress response attenuation
• Decreased morbidity

How do we treat pain?
• Understanding the pain pathway

Transduction- Mechanical stimulus into Electrical signal

Transmission- propagation of electrical signal
from nerves to brain

Modulation-altering or blocking the pain signal as
it traverse through the cord
• Is the way the brain alters the intensity of the signal travelling
up the ascending pathway depending upon the circumstances
surrounding the initiation of the nociceptive signal.
• Part of gate theory proposed by malzack& wall in 1965.

Perception-how the brain interprets the signal and
produces pain
• It occurs when the nociceptive signal is received by the
involved cortex.
• It has reached consciousness and now moves from
nociception to pain.

Pain assessment
• Valid & reliable assessment of pain is essential for effective
pain management.
• Yet the nature of pain makes objective measurements
impossible.
• Three main methods are currently used to measure pain
intensity: self report, behavioral, and physiological measures.
• Acute pain can be reliably assessed both @rest & during
movement with one dimensional scale such as
NRS/VAS/VRS(4 point)
• They function best for present pain intensity

NRS
• An NRS with numbers from 0 to
10 is more practical than a VAS,
• easier to understand for most
people, and
• does not need clear vision,
dexterity, paper, and pen.
• One can even determine the
intensity of pain accurately using
telephone interview

VRS
• NRS/VAS superior to
VRS because the verbal
categories may
corresponds to
different values on VAS
in the same patient on
different occasions
• Thus categorical pain
scales should be used
only as a coarse
screening instrument

Dynamic pain.
• Assessment of the intensity of acute pain at rest after surgery
is important for making the patient comfortable in bed.
• However, adequate relief of dynamic pain during mobilization,
deep breathing, and coughing is more important for reducing
risks of cardiopulmonary and thromboembolic complications
after surgery.
• Assessment of pain only at rest will not reveal differences
between more potent pain relieving methods, such as optimal
thoracic epidural analgesia, compared with less effective
epidurals or systemic opioid analgesia:

Contd,,
• Systemic opioids can make the patient comfortable, even
after major surgery, when resting in bed.
• However, severe dynamic pain provoked by movements
necessary to get the patient out of bed, and mobilizing
bronchial secretions by forceful coughing, cannot be relieved
by systemically administered potent opioids without causing
unacceptable adverse effects.

Neuropathic component of acute pain
• Better understanding the pain pathway leads to the The
possibility that such central sensitization of the spinal cord
may develop into chronic neuropathic pain after surgery.
• So it is important that we assess and treat signs of central
sensitization in acute pain.
• Assessment of mechanical allodynia, with von Frey filaments,
has shown that central sensitization of pain transmission
mechanisms after surgery can be suppressed by low-dose
ketamine & steroid.

In children – difficult process
• So we go for behavioral measures and/or with physiological
measures as a composite scale.
• The quality of these behaviors depends on the infant’s gestational
age, and maturity for ex: (Preterm or acutely ill infants, do not illicit
similar responses to pain due to illness and lack of energy.)
• Numerous scales are available depends on age group
For preterm to term infants:
1. Premature Infant Pain Profile (PIPP)
2. Neonatal Facial Coding System (NFCS)
3. Neonatal Infant Pain scale (NIPS)
4. Crying Requires Increased vital signs Expression Sleeplessness
(CRIES) - (32-60 wks)

Contd,,
Toddlers:
 Chidren’s Hospital of Eastern Ontario Pain Scale (CHEOPS)
 The Faces Legs Activity Cry Consolability Scale (FLACC)
 COMFORT Scale
Pre scholers:
 Faces Pain Scale by wong & baker (> 3 yr)
 Oucher scale
School age:
 Paediatric Pain Questionnaire
 Adolescent Pediatric Pain Tool (APPT).
Adolescents:
 The McGill Pain Questionnaire (MPQ).

During OR?
• Nociception/anti nociception balance by PDR
• Berthoud, V., Nguyen, M., Appriou, A. et al. Pupillometry pain index decreases
intraoperative sufentanyl administration in cardiac surgery: a prospective
randomized study. Sci Rep 10, 21056 (2020).

Skin Conductance algesimeter
• The SCA detects nociceptive pain fast and continuously, specific
to the individual, with higher sensitivity and specificity than
other available objective methods.- Storm H. Changes in skin
conductance as a tool to monitor nociceptive stimulation and pain. Curr Opin
Anaesthesiol. 2008 Dec;21(6):796-804. NFSC

normalized SCL (nSCL) = 100 × (SCL − average SCL in the pre-stimulus
period)/average SCL in the pre-stimulus period
SCL- average skin conductance value (μS) for 10 s
• whether the skin conductance monitor can distinguish a
stimulus that stimulates a sympathetic nerve but does not
cause pain from a stimulus that causes pain
• This study showed that nSCL is more useful for the detection
of physical pain than NFSC. - Sugimine, S., Saito, S. & Takazawa, T.
Normalized skin conductance level could differentiate physical pain stimuli
from other sympathetic stimuli. Sci Rep 10, 10950 (2020).

Qnox & QCoN
• One of the EEG based nociceptive measure contain dual
parameters. – based on the analysis of different frequency
bands in the EEG that are fed into ANFIS.
• The qCON was able to predict loss of consciousness such as
loss of verbal command and eyelash reflex while the qNOX
was able to better predict response to noxious stimulation
such as LMA insertion.-Melia U et al., Comparison of the qCON and qNOX
indices for the assessment of unconsciousness level and noxious stimulation
response during surgery. J Clin Monit Comput. 2017 Dec;31(6):1273-1281.

Ledowski T., Objective monitoring of nociception: a review of current commercial solutions British Journal of Anaesthesia, 123 (2):
e312ee321 (2019)

Types of analgesia
• Preemptive analgesia -focuses on postoperative pain control
and the prevention of central sensitization and chronic
neuropathic pain by providing analgesia administered
preoperatively.
• Preventive analgesia- reduces postoperative pain and
consumption of analgesics, and this appears to be the most
effective means of decreasing postoperative pain

Physical
modalities
approach
systemic
Physician
controlled
PCA
Regional
Surgical site
infiltration
IF plane
blocks

Opioid Receptor - Distributed throughout the brain & spinal cord;
and also outside the CNS –vascular tissues, cardiac, airway/lung, gut and cells
of the immune system.
•Rhodopsin family of GPCRs

Pure agonist
• Stimulates mu receptor,
• No ceiling effect
• Used for mod –severe pain
• Ex - morphine, fentanyl and its congeners
• Traditional time tested reliable analgesia.
• Cardiac stability
• Preconditioning effects

Morphine
• Morphine: prototype
• IV/IM/SC/oral
• Metabolism primarily by the liver and excreted primarily by the kidneys.
• Metabolites(M6G) may accumulate in patients receiving infusions or with
renal impairment
• Analgesic dose: 0.1-0.2mg/kg IV . 3months-1yr- 0.05-0.1mg/kg q 4-6hrs
• Slow rise to peak effect 10-20mins
• P/o- 5-15mg onset-30min,
• Epidural - 3-5mg, IT – 4-10mcg/kg
• Infusion – 50mcg/kg f/b 20-40mcg/kg/hr
• PCA- 1-2mg lockout 5-15min no background
• T1/2 1-3hr
• ↓SBP- H2 release or brady

• Fentanyl – 60-80 * potent, highly lipid soluble,
• IV/IN/TD
• Lipophilic drug therefore may result in accumulation
• Metabolised almost exclusively by liver, less than 10% un-metabolised
• Excreted by kidneys
• Dose 1-2mcg/kg
• Onset-immediate, DOA-15mins t1/2-1.5hrs
• Infusion 1-2mcg/kg/hr
• PCA- background infusion-1-2mcg/kg/hr bolus 0.5-1mcg/kg, lockout
interval 15-20 mins.
• Epi- 25-50mcg/ 2-4mcg/ml, IT-10-25mcg

• Sufentanil- 10* fentanyl
• 0.1-0.3mcg/kg
• 0.1-0.6mcg/kg/hr
• Epi-10-30mcg, 0.75-1.0 μg/mL, IT-1.5-5 μg
• Alfenatnil- 5-10 times less potent.
• But highly lipid soluble effect< 1 min
• 10-20mcg/kg
• 15-45mcg/kg/hr
• Remifentanil- equal to fentanyl, very fast onset,
• 0.05–1 μg/Kg/min only IV

Tramadol
• centrally acting analgesic that has moderate affinity for mu
receptors and weak kappa & delta affinity
• Enhances the descending inhibitory pathway via NE & 5-HT (inhibit
reuptake)
• 5 to 10 times less potent than morphine(more
emetogenic/delirium )
• Dose: 50-100mgIV q6th hrly , IT-10-50 mg, EPI-1-2mg/kg, PNB-1-5mg/kg
• Max dose 400mg/24hr
• Tramadol + paracetamol combination along with PCA morphine
improves analgesia and reduces morphine requirement up to 50%
after CABG, compared with morphine PCA alone. Altun D et al., The effect of tramadol
plus paracetamol on consumption of morphine after coronary artery bypass grafting J clin anesth 2017 feb;36:189-193.

Adv effects
• PONV, pruritus, constipation, urinary retention, sedation,
respiratory depression, tolerance & dependence
• ICU-associated delirium, prolonged mechanical ventilation, delayed
intestinal recovery after surgery (POI)& OIH.
• In 1996 APS- instituted that pain as the 5th vital sign campaign, but
subsequently all other societies like AMA, TJC have withdrawn their
advocacy of this campaign due to growing opioid crisis.
• Evidence suggests an association between intraoperative opioid
administration and subsequent postoperative opioid use as well as
the incidence of postoperative complications,(opioid paradox)

APS guidelines
• The panel recommends oral over IV administration of opioids for
postoperative analgesia in patients who can use the oral route
(strong recommendation, moderate quality evidence).
• The panel recommends that IV patient-controlled analgesia (PCA)
be used for postoperative systemic analgesia when the parenteral
route is needed (strong recommendation, moderate-quality
evidence).
• Preoperative administration of opioids is not recommended as an
intervention to decrease postoperative pain and/or opioid
consumption.
• The panel recommends that clinicians avoid using the intramuscular
route for the administration of analgesics for management of
postoperative pain(strong recommendation, moderate-quality
evidence)

OFCA – A flash in the pan?
• Nonopioid interventions employed as part of an ERP for
cardiac surgery were associated with a reduction of
intraoperative opioid administration.
• Low and ultralow opioid use was not associated with
significant differences in postoperative outcomes.-Grant MC et al.,-
Opioid-Sparing Cardiac Anesthesia: Secondary Analysis of an Enhanced Recovery Program for Cardiac
Surgery anesth analg 2020;131:1852-61.
• synergistic effect and multiple action site of the drugs used in
the OFA-group could improve post-operative pain lowering
the incidence of the side effects of each drug.
• Moreover, the additive anti-inflammatory effects of each drug
may lower the most frequent postoperative complications –
Aguerreche, C., Cadier, G., Beurton, A. et al. Feasibility and postoperative opioid sparing effect of an
opioid-free anaesthesia in adult cardiac surgery: a retrospective study. BMC Anesthesiol 21, 166 (2021)

Evidence
• Cox 2 I not recommended after CABG – class III ACC/AHA
• FDA 2005 black box warning except aspirin immediate after CABG.
• Use declined but still persists.
• In [patients undergoing cardiac surgery], does [the use NSAIDs]
increase the risk of [renal failure]?
• The meta-analysis of 1065 patients across 20 RCTs - Acharya M Dunning J.,
Does the use of non-steroidal anti-inflammatory drugs after cardiac surgery increase the risk of renal
failure?, Interactive CardioVascular and Thoracic Surgery, 2010:9(11):461–67.
• conclude that NSAIDs are not associated with an increased risk of
renal failure after cardiac surgery when administered at optimal
‘renal’ doses, within early postoperative settings, to patients at low-
risk of renal dysfunction in whom NSAIDs are not contraindicated.

• Saini A, Maher KO, Deshpande SR. Nonopioid analgesics for perioperative
and cardiac surgery pain in children: Current evidence and knowledge
gaps. Ann Pediatr Cardiol. 2020;13(1):46-55.
• The purpose of this review is to present the available
literature on the use of non opioid analgesics such as
NSAIDs in post-cardiac surgery pediatric patients, mainly
to focus on patients <1 year of age, and to provide the
foundation for future research.
• Non-opioid medications appear to show promise for
analgesia in infants undergoing cardiac surgery, with
ketorolac being the most potent agent as a potential
substitute for opioids

ketorolac
• IM/IV potent analgesic
• potentiates the anti nociceptive actions of opioids (25-50% ↓
morphine)
• Time to peak IV-5min, IM-20min
• T1/2 – 4-6hrs
• 0.5mg/kg q6hr (PRN)
• EC50=0.37mg/l

• A total of 1,309 cardiac surgical patients (78.1% coronary
bypass, 28.0% valve) - 488 received -Ketorolac – it appears to
be well-tolerated for use when administered selectively after
cardiac surgery Oliveri L, Jerzewski K, Kulik A. Black box warning: is ketorolac safe for
use after cardiac surgery? J Cardiothorac Vasc Anesth. 2014 Apr;28(2):274-9.
• No association was found between continuous infusion
ketorolac and increased risk of mortality, MI, or bleeding
events in postoperative CABG patients.
• Considerations to differences in baseline characteristics must
be made when interpreting results.Howard ML, Warhurst RD, Sheehan C. Safety
of Continuous Infusion Ketorolac in Postoperative Coronary Artery Bypass Graft Surgery Patients.
Pharmacy (Basel). 2016 Jun 28;4(3):22

In children
• Current literature supports the safe use of this medication at 0.5
mg/kg per dose IV every 6 hours for 48 hours following cardiac
surgery
• Ketorolac is contraindicated in those with a history of renal failure;
taking concurrent nephrotoxic, NSAID, & clinically significant
bleeding during or immediately following the surgery; or with a
history of GI bleeding. Jalkut MK. Ketorolac as an analgesic agent for infants and children
after cardiac surgery: safety profile and appropriate patient selection. AACN Adv Crit Care. 2014
Jan-Mar;25(1):23-30
• Intravenous ketorolac appears to be safe when used in infants <
6months of age with biventricular circulations following
cardiothoracic surgery.
• Ketorolac as used in these patients does not decrease the use of
standard analgesic therapy.-Dawkins TN, Barclay CA, Gardiner RL, Krawczeski CD.
Safety of intravenous use of ketorolac in infants following cardiothoracic surgery. Cardiol
Young. 2009 Feb;19(1):105-8

Ibuprofen
• Oral/rectal/IV
• Tmax – 2hr tab, suspension 15min,
• T1/2 -2 hr
• 10mg/kg q 6hr
• Ceiling effect @ 400-1200mg
• Ketoprofen: oral/rectal/iv
• IV 1mg/kg
• T1/2-1.3hr

PCM
• Weak analgesic in comp with NSAID
• Oral/rectal/IV
• 10-15mg/kg 6-8th hrly
• Tmax-45-60min
• T1/2- 172min
• Limit to 4g/24hr
• Ceiling @ 1gm
• Negmeldeen F et al., Intravenous acetaminophen analgesia after cardiac surgery: A
randomized, blinded, controlled superiority trial, The Journal of Thoracic and
Cardiovascular Surgery, 2016;152(3):881-89. –
• IV acetaminophen reduced pain after cardiac surgery, but not opioid
consumption.
• IV acetaminophen can be an effective analgesic adjunct in patients
recovering from median sternotomy.

IV vs ORAL
• achieves a higher plasma concentration when administered IV.
• but this does not necessarily improve postoperative pain scores
when compared to the oral or rectal route.
• Intravenous acetaminophen is not sufficient for pain relief when
used as mono-therapy following adult cardiac operations.
• Authors believe the current role for IV acetaminophen after cardiac
surgery should be limited only to select patient who are unable to
tolerate oral analgesia during the first 24-48 postoperative hours. –
• DJ Douzjian, A Kulik -Old drug, new route: a systematic review of
intravenous acetaminophen after adult cardiac surgery J card vasc
anesth 2016 mar;16:

The panel recommends that clinicians offer multimodalanalgesia, or the use of a variety of analgesic medications and
techniques combined with non pharmacological of postoperative pain in children and adults (strongrecommendation,
high-quality evidence).

Multimodal or “balanced” analgesia is a method of
analgesia which considers the multistep nature of pain
– throughout the periop period.
Goals:
• Create additive analgesia from administration of different classes of
analgesic methods.
• Decrease the dose of each analgesic modality.
• Experience less unwanted side effects of each drug or non-drug
method.
• Counteract pain at different levels, i.e., at the level of CNS, spinal
cord, peripheral nerves, wound site, etc.
• However, this approach has very important considerations due to
the specific type of cardiac procedures.
• For example, neuraxial analgesia has its own considerations &
systemic drugs on CV dynamics

Pre op- α2δ ligands (gabapentinoids)

• 7 trials involving 463 patients were listed
• Oral pregabalin (150mg)for cardiac surgery patients can
effectively reduce the patient's 24-hour morphine
consumption after surgery, shorten the patient's hospital stay,
and is more conducive to early postoperative recovery.- Wang
XX et al., Oral Pregabalin in Cardiac Surgery: A Systematic Review and Meta-
Analysis of Randomized Controlled Trials. Biomed Res Int. 2021 Mar 3.
• Four RCTs each for gabapentin and pregabalin have been
included in this systematic review.
• Despite lower pain scores in the postoperative period, there is
insufficient evidence to recommend routine use of
gabapentin and pregabalin to reduce opioid consumption in
the cardiac surgical patients- Maitra S et al., Perioperative gabapentin
and pregabalin in cardiac surgery: a systematic review and meta-analysis. Rev Bras
Anestesiol. 2017 May-Jun;67(3):294-304

Ketamine -Sub anesthetic dose- anti-hyperalgesic & anti-nociceptive effects.
Onset 30s T1/2 2.5hr
Iv/Im/oral/IN/neuraxial
Cst1/2 40 min after 8 hr

• This trial showed no improvement in overall pain scores
compared to placebo; however patient satisfaction was
improved, and there was significant postoperative opioid
sparing- Lahtinen P, Kokki H, Hakala T, Hynynen M. S(+)-ketamine as an analgesic adjunct
reduces opioid consumption after cardiac surgery. Anesth Analg. 2004;99:1295–301
• ketamine could prove to be a beneficial adjunct in preventing
chronic poststernotomy pain and depression, which occur at
relatively high rates after cardiac surgery and also attenuates
inflammatory response to CPB-Mazzeffi M, Johnson K, Paciullo C. Ketamine in
adult cardiac surgery and the cardiac surgery Intensive Care Unit: an evidence-based clinical
review. Ann Card Anaesth. 2015;18(2):202-209.
• A constant rate infusion of ketamine supplemented with
midazolam provided satisfactory pain relief and adequate
sedation in small children after open heart surgery.
• Psychomimetic side effects were not seen and were possibly
suppressed by the supplementary midazolam doses - Hartvig P,
Larsson E, Joachimsson PO. Postoperative analgesia and sedation following pediatric cardiac
surgery using a constant infusion of ketamine. J Cardiothorac Vasc Anesth. 1993 Apr;7(2):148-
53.

Dexmed
It produces sedation and weak analgesia by increasing GABA inhibition in the
CNS and spinal cord(↓sympathetic flow)
Cst1/2 4hr after 8 hr infusion
IT: 5-10 μg, Epi: 1 μg/kg, PNB-20-150 μg

Dexmedetomidine infusion even without loading dose provides
safe, effective adjunct analgesia, reduces narcotic consumption,
and showed a reduced trend of delirium incidence without
undesirable hemodynamic effects in the cardiac surgery patients-
Priye S et al., Dexmedetomidine as an adjunct in postoperative analgesia following cardiac surgery: A
randomized, double-blind study. Saudi J Anaesth. 2015;9(4):353-58.
Dexmedetomidine has anesthesia-sparing effects, it decreases
MAP, HR and with reasonable analgesic effect in pediatric cardiac
surgery. El-morsy GZ et al., Dexmedetomidine; an adjuvant drug for fast track technique in pediatric
cardiac surgery Egypt J anesth 2014;9(30):347-351.

IV lidocaine is gaining traction as a postoperative analgesic because of its anti-
inflammatory and anti-hyperalgesia properties.
These effects occur through a dose-dependent inhibition of sodium, potassium,
and calcium channels and G coupled protein and NMDA receptors.
adjunct to analgesia for both acute postoperative and chronic pain and as a cardio
protective agent in the setting of myocardial ischemia and reperfusion injury.

• Lee et al. found that intraoperative IV lidocaine reduced
remifentanil requirements, in addition to decreasing
myocardial injury as evidenced through cardiac enzyme
release, in patients undergoing off-pump CABG surgery.
• 2% lidocaine placed topically on chest tubes prior to
intraoperative insertion intrapleurally was associated with
significantly lower pain scores and significant improvements
in FEV1 (certainty in evidence very low).
• However, lidocaine infusions were not associated with
significant changes in pain scores - Boswell MR Moman, R.N
Burtoft M. et al. Lidocaine for postoperative pain after cardiac
surgery: a systematic review. J Cardiothorac Surg 16, 157
(2021).

Magnesium is a calcium and an NMDA-receptor antagonist and
can modify important mechanisms of nociception

• Moderate reduction of overall remifentanil consumption after
cardiac surgery by co-administered iv magnesium gluconate.
• A more pronounced opioid-sparing effect might be found with
higher pain scores or with a larger dose of magnesium without side
effects steinlechner B et al., Magnesium moderately decreases remifentanil dosage
required for pain management after cardiac surgery 2006 apr;96:444-49.
• Mg significantly decreases the incidence of all type of postcardiac
surgery arrhythmia and decrease the severity of postoperative pain
and agitation. Hamed MA, Farhan FS. The Efficacy of Magnesium Sulfate in
Reduction of Post Cardiac Surgery Arrhythmia, Agitation and Pain: A randomized
controlled study Anesth Pain Res. 2018; 2(2): 1-6

Steroids
• Murphy et al. demonstrated that the administration of
dexamethasone decreased morphine consumption and the ICU
length of stay QoR In elective CS patients
• Turan et al use of methylprednisolone for persistent incisional pain
after cardiac surgery(SIRS) trial failed to show any difference in the
incidence of persistent incisional pain
• Yet in follow up only a total of 10 out of 1150patients had
neuropathic pain in the SIRS sub study at 6 months
• other important factors such as differences in surgical and
anesthetic techniques and postoperative analgesic management,
which were not controlled, could have played an important role-
Shanthanna H, Kehlet H; Steroids Do Not Reduce Persistent Pain
after Cardiac Surgery: Should This Be the End of the Question or the
Beginning of Newer Questions?. Anesthesiology 2016; 125:423–425

Opioid sparing in CS
Intervention:
• 1g PCM/ gabapentin 600mg, PO
• Ketamine intraoperative infusion; 0.2–0.3 mg/kg/hr
• Dexmedetomidine 0.2–1.5 μg/kg/h; administered at the time of CPB till
ICU
• Serratus Anterior Plane block- at the end of surgery bupivacaine 0.375%–
0.5%, 20–30 mL bilaterally)
Conclusion:
• Non-opioid interventions employed as part of an ERP for
cardiac surgery were associated with a reduction of
intraoperative opioid administration.
• Low and ultralow opioid use was not associated with
significant differences in postoperative outcomes.
Grant MC et al., Opioid-Sparing Cardiac Anesthesia: Secondary Analysis of an Enhanced Recovery Program
for Cardiac Surgery anesth analg 2020 dec 131;1852-61.

OFA in CS
• dexamethasone (0.1 mg/kg ), ketamine (0.3–0.5 mg/kg ),
lidocaine (1.5 mg/kg bolus 15 min before the start of
propofol) and propofol (0.4–2 mg/kg) until the loss-of-eyelash
reflex.
• Lidocaine was continuously administered at 1.5 mg/kg/h until
the end of surgery
• Results:-
1. Lower postoperative morphine consumption;
2. Higher operative use of antihypertensive agents;(less
hypnotic effect?/ vasoconstrictive effect?)
3. decrease in MV duration &shorter ICU stays.
• No adverse effects related to multiple drug usage.
Guinot et al. Effect of opioid-free anaesthesia on postoperative period in cardiac surgery: a
retrospective matched case-control study BMC Anesthesiology (2019) 19:136

Regional techniques
TEA
Benefits
• Efficient suppression of stress
response Improved myocardial blood
flow & imp function.
• Relatively selective Thoracic
sympathectomy
• Decreased incidence of cardiac
arrhythmias mainly after improved
myocardial perfusion status.
• “awake” off-pump coronary bypass
surgery or some other percutaneous
valve replacements using TEA as the
main anesthetic method –
• chakravarthy M Technique of awake
cardiac surgery Techniques in Regional
Anesthesia and Pain Management
Jan2008 ;12(1):87-98
Risk
• “epidural hematoma” which could
heavily outweigh the above detailed
list of benefits
• Incidence 1:1500 to 1:150,000
• during the postoperative period,
when trying to normalize the
coagulation profile in order to
remove the catheter,↑ risk of
thromboembolic events.
• occurrence of epidural hematoma
and its neurologic complications is a
catastrophe.

Epidural analgesia for adults undergoing cardiac surgery with or without
cardiopulmonary bypass-CDSR
guay J kopp S. 1-3-2019
on perioperative mortality and cardiac, pulmonary, or
neurological morbidity.
• 69 trials with 4860 participants: 2404 given epidural analgesia
and 2456 receiving comparators (systemic analgesia,
peripheral nerve block, intrapleural analgesia, or wound
infiltration
• Compared with systemic analgesia, TEA may reduce the risk of
myocardial infarction, respiratory depression, AF as well as
the duration of MV & pain, in adults undergoing cardiac
surgery.
• There may be little or no difference in mortality, pneumonia.

• Epidural haematoma, and effects on cerebrovascular accident
are uncertain. (very low quality GRADE)
• Evidence is insufficient to show the effects of epidural
analgesia compared with peripheral nerve blocks, intrapleural
analgesia, or wound infiltration
• ASRA (joint recommendation with the European Society of
Anaesthesiology) stated: "Currently, insufficient data and
experience are available to determine if the risk of neuraxial
hematoma is increased when combining neuraxial techniques
with the full anticoagulation of cardiac surgery" (Horlocker
2018)

2010 ASRA & 2009 the Scandinavian Society of Anaesthesiology
and Intensive Care Medicine
1. Do not use neuraxial blocks if the patient has a “known underlying
coagulopathy” no matter what is the etiology.
2. If the epidural needle tap is traumatic, surgery should be postponed for
at least 24 h.
3. Time interval from the end of the epidural technique (including needle
tap, drug administration, etc.) until start of systemic heparinization
should be at least more than 60 min.
4. The clinicians should adhere strictly to the administration doses of
heparin and its reversal agents (try strictly to administer as low as
possible doses of heparin which are adjusted for the “shortest duration”
for the desired “therapeutic objective”).
5. Removing the epidural catheter is permitted only when the coagulation
profile tests are resumed to normal values; besides, catheter removal
should be followed by strict control of signs and symptoms for any
potential epidural hematoma

Contd,,,
• There is no standard drug regimen for TEA
• It varies on an institutional basis. (LA/opioid)
• The theoretic risk of epidural hematoma can be minimized by
using standard precautions to ensure normal hemostasis
before catheter insertion and removal.
• Thus, TEA in cardiac surgery is a useful technique provided the
risk-benefit ratio is individualized.
• It is good for selected patients, such as those with morbid
obesity, COPD, or in geriatric patients, but it will remains
controversial.

PVB
• The main benefits of TPVB compared with TEA could be
considered as:
• Being less invasive.
• Very lower risk for epidural hematoma formation.
• Less hemodynamic derangement (albeit some degrees of
sympathetic block exists).
• Fewer contraindications.
• Easier technique – USG guided

• USG – PVB is safe and effective method for relieving post-
cardiac surgery sternotomy pain compared with thoracic
epidural analgesia but not superior to it - El Shora HA et al., Bilateral
Paravertebral Block versus Thoracic Epidural Analgesia for Pain Control Post-Cardiac
Surgery: A Randomized Controlled Trial. Thorac Cardiovasc Surg. 2020 Aug;68(5):410-
416.
• This meta-analysis has shown that continuous PVB reduced
the incidence of nausea and vomiting, hypotension and
urinary retention compared with epidural analgesia.
• The continuous PVB offers equivalent analgesia to epidural
analgesia in cardiothoracic surgeries- Scarfe AJ et al.,Continuous
paravertebral block for post-cardiothoracic surgery analgesia: a systematic review and meta-
analysis, European Journal of Cardio-Thoracic Surgery, Dec 2016;50(6):1010–1018.

fentanyl: 1-2mcg/ml
clonidine:0.8-1.5mcg/ml

Complications of neuraxial opioids:
Respiratory Depression Frequent (up to 7%)
Pruritus Very common (5.1 – 37%)
Urinary Retention Likely increased
Nausea and Vomiting Very common (≥25%)
Intrathecal morphine increases incidence of Vasoplegia.

TEA vs spinal in CS
Kowalewski R., Neuraxial anesthesia for cardiac surgery: thoracic epidural and high spinal anesthesia - why is it different?. HSR Proc
Intensive Care Cardiovasc Anesth. 2011;3(1):25-28.

Intra-thecal- 1:220000
• Intrathecal morphine(400mcg) administration did not significantly alter
pulmonary function; however, it improved patient analgesia and reduced
morphine consumption and morphine plasma concentration- Dos Santos LM,
Intrathecal morphine plus general anesthesia in cardiac surgery: effects on pulmonary function, postoperative
analgesia, and plasma morphine concentration. Clinics (Sao Paulo). 2009;64(4):279-85.
In [patients undergoing cardiac surgery], is [intrathecal morphine superior to
iv morphine] for [complication free analgesia] ?
• The most consistently reported benefits of IT morphine are reduced pain
scores, & IV morphine dose.
• Some studies report benefits of shorter time to extubation, improved
postoperative lung function and shorter ICU and hospital stays,
• No spinal haematomas were reported, however, patients at high risk of
bleeding were excluded.
• Opioid-related complications remained comparable to patients receiving
only IV morphine postoperatively Richardson L, Is intrathecal morphine of benefit to patients
undergoing cardiac surgery, Interactive CardioVascular and Thoracic Surgery, Jan2009;8,: Pages:117–122.
Zangrillo A.Spinal analgesia in cardiac surgery: A meta-analysis of randomized controlled trials. J Cardiothorac Vasc Anesth.
2009; 23: 813-821

• Dosing before surgery is effective provided the morphine dose is
greater than 6 μg/kg @ cost of prolonged ventilation.
• Some patients had a delayed respiratory depression after tracheal
extubation, related to the combined use of IT & IV morphine.
Adjuvants?
• Clonidine 1-2 mcg/kg
• combination of intrathecal clonidine and morphine gives effective
control of postoperative pain & facilitate fast-track cardiac
anaesthesia-Lena P Intrathecal morphine and clonidine for coronary
artery bypass grafting Br J anesth 2003;3(90):300-03.
• ITB , when combined with general anesthesia, resulted in less beta-
receptor dysfunction and a lower stress response during coronary artery
bypass graft surgery- Lee TWR., Effects on β-Adrenergic Receptor Function, Stress Response,
and Hemodynamics. Anesthesiology 2003; 98:499

Caudal epidural
• Caudal analgesia is the alternative attractive technique in pediatric
cardiac sx.
• Vakamudi M et al., compared efficacy and safety of caudal, thoracic
epidural, and intravenous analgesia in paediatric cardiac surgery.
• RA group had lesser pain scores.
• TEA had lesser duration of MV & ICU stay compared to caudal and
IV group.
• TEA & caudal blocks can be given safely in paediatric cardiac
surgery with RACHS score less than 3.

Maharramova M, Taylor K. A Systematic Review of Caudal Anesthesia and
Postoperative Outcomes in Pediatric Cardiac Surgery Patients. Seminars in
Cardiothoracic and Vascular Anesthesia. 2019;23(2):237-247.
• The total number of patients was 2159 in 17 studies
• Caudal medications included dexmedetomidine, bupivacaine,
sufentanil, morphine, fentanyl, and neostigmine
• Caudal anesthesia may be favorable for early extubation,
improved pain, and hemodynamics and reduced LOS.
• Yet the data quality in this review is too poor to make
recommendations regarding incorporation of caudal
anesthesia into clinical practice

• Fascial plane blocks are
considered “volume blocks,”
• ropivacaine(0.1-0.2%)
• bupivacaine (0.0625-o.125%)
• 10-40ml
• based on the patient’s
maximum allowed mg dose.
• Although adjuvants used in
NA technique, in IF plane
continuous catheter-based
delivery analgesia to achieve
prolonged block duration
rather adjuvants.

Kumar KN, Kalyane RN, Singh NG, Nagaraja PS, Krishna M, Babu B et
al., Efficacy of bilateral pectoralis nerve block for ultrafast tracking
and postoperative pain management in cardiac surgery. Ann Card
Anaesth 2018;21:333-

Berthoud, V., Ellouze, O., Nguyen, M. et al. Serratus anterior plane
block for minimal invasive heart surgery. BMC Anesthesiol 18, 144
(2018)

Krishna SN, Chauhan S, Bhoi D, Kaushal B, Hasija S, Sangdup T, Bisoi AK. Bilateral
Erector Spinae Plane Block for Acute Post-Surgical Pain in Adult Cardiac Surgical
Patients: A Randomized Controlled Trial. J Cardiothorac Vasc Anesth. 2019
Feb;33(2):368-375.

Nobukani K. Retrolaminar versus epidural block for postoperative
analgesia after minor video-assisted thoracic surgery: a
retrospective, matched, non-inferiority study. J Thorac Dis
2021;13(5):2758-2767

Fujii S, Roche M, Jones PM, Vissa D, Bainbridge D, Zhou JR.
Transversus thoracis muscle plane block in cardiac surgery: a
pilot feasibility study. Reg Anesth Pain Med. 2019
May;44(5):556-560

Scimia, P., Fusco, P., Tedesco, M., & Sepolvere, G. Bilateral ultrasound-
guided parasternal block for postoperative analgesia in cardiac surgery:
could it be the safest strategy? Regional Anesthesia & Pain Medicine, 2019–
100872.

• ESP block had a comparable pain scores with TEA, and
hence proved to be an effective alternative to TEA in an
adult cardiac surgery for the perioperative pain
management and fast tracking. Nagaraja PS, Ragavendran S, Singh NG, 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;21(3):323-27.
• Continuous ESP block produced safe and effective analgesia
for 48 h after extubation following CABG.
• It also reduced perioperative opioid consumption and
allowed early tracheal extubation without major adverse
effects. Sanaa F et al. Bilateral continuous erector spinae block versus multimodal
intravenous analgesia in coronary bypass surgery. A Randomized Trial, Egyptian Journal of
Anaesthesia, 37:1, 152-158,
• The addition of PECS blocks to ESP block led to reduced
consumption of oxycodone via PCA, reduced pain intensity
on VAS, and increased patient satisfaction with pain
management in patients undergoing mitral/tricuspid valve
repair via mini-thoracotomy Gawęda, B., Borys, M., Belina, B. et
al. Postoperative pain treatment with erector spinae plane block and pectoralis nerve blocks in
patients undergoing mitral/tricuspid valve repair — a randomized controlled trial. BMC
Anesthesiol 20, 51 (2020).

other
• Parasternal block (before sternal wire) and local anesthetic
infiltration of the sternotomy wound and mediastinal tube
sites with
• levobupivacaine can be a useful analgesic adjunct for
patients who are expected to undergo early tracheal
extubation after cardiac surgery- McDonald SB et al. Parasternal block and
local anesthetic infiltration with levobupivacaine after cardiac surgery with desflurane: the
effect on postoperative pain, pulmonary function, and tracheal extubation times. Anesth
Analg. 2005 Jan;100(1):25-32.
• Continuous presternal bupivacaine and magnesium infusion
(0.125% bupivacaine and 5% magnesium sulfate (3 ml/h for
48 hours)resulted in better postoperative analgesia
• than both presternal bupivacaine alone or conventional
analgesic groups. Kamel EZ et al. Pain alleviation in patients undergoing cardiac
surgery; presternal local anesthetic and magnesium infiltration versus conventional
intravenous analgesia: a randomized double-blind study. Korean J Pain. 2018 Apr;31(2):93-
101

• IPA is a safe and effective technique for postop analgesia
after MIDCAB surgery and has a low complication rate
compared with TEA.
• Careful positioning, chest tube clamping, and anchoring of
the catheter are mandatory for IPA to be effective - Mehta Y, et
al. "A comparative evaluation of intrapleural and thoracic epidural analgesia for
postoperative pain relief after minimally invasive direct coronary artery bypass surgery." J
cardiac and vas anesthesia 12.2 (1998): 162-165.
• preemptive analgesia with bilateral intrapleural block using
bupivacaine provided relatively less painful conditions
during the first 24 h after surgery, but it did not improve the
clinical outcome- Mansouri M et al. Randomized controlled trial of bilateral
intrapleural block in cardiac surgery. Asian Cardiovascular and Thoracic Annals.
2011;19(2):133-138.

TDS
• Compared to oral or systemic dosage systems, TDDS can offer a
controlled release of the drugs which could reduce
1) the first-pass metabolism effects,
2) lessen systemic side effects,
3) improve the dosage efficacy & enhance patient compliance,
• Yet, limited by the excellent barrier function of the skin, in
particular the stratum corneum
• drugs are expected to be highly potent, are lipophilic, and have a
low molecular mass (<600 Da) can pass
• To improve multiple techniques tried but recently nanoparticles are
upcoming,

Buprenorphine
• 0.3 mg = to 10 mg morphine
• The peak-effect was achieved at 48-72 hours
• Oral morphine equivalent <30 mg/day: Initiate with 5 mcg/hr patch
• Oral morphine equivalent 30-80 mg/day: Initiate with 10 mcg/hr
patch, never exceed 20mcg/hr
• May supplement with prompt-acting opioid and nonopioid
analgesic for break-through pain
• 7 days change over.
• T1/2 = 20-36hrs.
Risk: greater risks of overdose and death with ER opioid formulations

TD Fentanyl
• 12-100mcg/hr, q 72hr
• Tmax -16-24hr
• T1/2 = ≥17 hr
• Gradually titrate the dose, (eg, 50% dosage reduction q6days),
while monitoring carefully for signs and symptoms of withdrawal
• Avoid in severe renal/hepatic impairment
• youngsuk. preoperative TFP attenuated the increase in IL-6 levels
after surgery and provided similar analgesic effects to continuous
intravenous fentanyl infusion.
• Therefore, preemptive TFP may have influence on pro-
inflammatory reactions during the perioperative period, and may
be effective background analgesia. Surgical Laparoscopy, Endoscopy &
Percutaneous Techniques: Oct 2019 ;29:339-343

PCA
• Administration of parenteral opioids, through microprocessor-
controlled infusion pump
Adv:
• Increased patient autonomy
• Increased concordance between analgesics and patient
demands
• Decreased frequency of opioid complications including
nausea and vomiting
• maintaining a steady drug concentration in the serum

• As a standard, use a baseline analgesic infusion which should
be added to PCA in order to prevent unwanted effect.
• Apply a baseline-appropriate PCA dose accompanied with
lockout interval, and adjust it for each patient
• Beware of respiratory depression which should be always
considered as a potential risk.
• Try to increase patient cooperation as much as possible;
insufficient patient cooperation leads to ineffectiveness of
PCA;
• In case of impaired patient cooperation, PCA use should be
discouraged

APS recommendations
• The panel recommends that clinicians consider TENS as an
adjunct to other postoperative pain treatments (weak
recommendation, moderate-quality evidence).
• The panel can neither recommend nor discourage
acupuncture, massage, or cold therapy as adjuncts to other
postoperative pain treatments (insufficient evidence).
• The panel recommends that clinicians consider the use of
cognitive–behavioral modalities in adults as part of a
multimodal approach (weak recommendation, moderate-
quality evidence).

Recent advances
1. Molecular Mechanisms – understanding the
central sensitization
2. Pharmaceutical products – Depodur, Exparel
etc..
3. Routes and modes of delivery –various PCA
4. Other modes of analgesia

Depodur
• ER formulation of morphine in a liposomal carrier, specific for
epidural (lumbar)administration
• DepoDur™ is not intended for IV / IT, or IM administration
• Dose : 5-25mg
• up to 48 hours duration with similar adv effects profile.
• The potential of providing extended analgesia without an epidural
catheter or IV-PCA pump is very desirable
• There should be at least a 15-minute waiting period after a
standard 3 ml epidural test dose of lidocaine with epinephrine.

• In studies of drug interactions with DepoDur™ local
anesthetics increased the release of morphine from the
carrier.
• Currently, DepoDur™ can not be given following a true
epidural with local anesthetics since the effect on morphine
release is unknown
• no other drug should be placed in the epidural space within
48 hours of DepoDur™ administration because the effect on
the release profile of morphine from the carrier (DepoFoam)
is unknown.

Make old drug new
• Liposome or polymer encapsulation of local anesthetics are
being formulated.
• Liposomes are microscopic phospholipid- bilayered vesicles
that are biocompatible, biodegradable, and non-
immumnogenic ex: lip bupivacaine – 72 hrs
• Recently nanoparticles, composed of biodegradable
polymers(nano-medicine) They have some advantages over
liposomes in terms of stability both during storage and in vivo

Nitroxyparacetamol (or
nitroacetaminophen)
• new, potent NO-releasing version of paracetamol.
• The described mechanism of action in the spinal cord(↓ wind
up) may differ from that of paracetamol, & may be less
hepatotoxic
• 3–20 times more potent
• NO appears to produce these beneficial actions through
several mechanisms, including the suppression of synthesis of
several proinflammatory cytokines,
• and may be per se a useful therapy for paracetamol-induced
liver damage.
I. Power, Recent advances in postoperative pain therapy, BJA: British Journal of Anaesthesia,
July 2005;95:43–51

PCRA
• PCRA – Incisional
• IN-Intranasal (IN) opioids, either in the form of a dry powder or saline
solution, are delivered using a syringe, nasal spray or dropper, or nebulized
inhaler.
• This (especially fentanyl) bypasses the hepatic first-pass effect and
because of the excellent perfusion of the nasal mucosa, displays rapid
absorption and rise in plasma concentration
• TPA(AeroLEF™(aerosolized liposome-encapsulated Fentanyl; YM
BioSciences Inc., Ontario,Canada)-simple and noninvasive route of
administration,
• rapid onset & sustained effect, and self-titratable dosing for the
treatment of acute and breakthrough pain.
• Using AeroLEF™, patients can identify and select a personalized dose for
each pain episode, achieving both rapid onset and extended duration of
analgesia.
• However, it is still a long way from being used in clinical practice.

Capsaicin
• Non narcotic and act peripherally as a TRPV-1 agonist(present on c
fibers)
• The activation of the TRPV receptors releases high intensity
impulses & releases substance P, which results in the initial phase of
burning.
• Continued release of substance P in the presence of capsaicin leads
to the depletion of capsaicin and a subsequent decrease in C fiber
activation
• Cream(8%) & injectable under phase 3 trial
• C/I – hypersensitivity relative: < 2 yrs, ↑LFT, ACEi,

Tapentadol
• centrally acting analgesic with a unique dual mode of action
as an agonist at the μ- opioid receptor & NE reuptake inhibitor
• Immediate release oral preparations of 50, 75 100 mg
(Nucynta®, Johnson & Johnson) –q6hr
• Max daily dose-600-700mg
• FDA approved for >18yrs
• Potency between tramadol and morphine,
• C/I-bronchial asthma, paralytic ileus, MAOI.
• Serotonin syndrome can develop with the use of tapentadol,

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