A comprehensive guide to peri-operative pain management and sedation for the general surgeon. With a focus on drug availability in the state healthcare sector South Africa

1. Pain control and sedation for
surgeons
Dr Marguerite Barnard
University of Pretoria, South Africa

2. Defining pain
• An unpleasant sensation that can
range from mild, localized
discomfort to agony, with both
physical and emotional
components.
• The physical part of pain results
from nerve stimulation.
• Pain may be contained to a discrete
area, or it can be more diffuse
• Latin origin “poena” meaning
penalty of fine.

3. Physiology of pain

4. Reasons for ICU patients in pain
• Primary pathology - burns, traumatic injuries, fractures, wounds
• Complications of original condition or new problems - bowel
perforation, ischemic bowel, pancreatitis
• Sepsis - Abscesses, skin inflammation, wound infection
• Support systems & monitoring—peripheral, central venous line
insertions, catheters, drains, regular suctioning, dressing changes,
physiotharapy
• Tissue hypoxia as a result of low cardiac output, low O2 saturation,
fall in HB result in MI
• Painfull joints, pressure points, pain on changing, position in bed

5. Complications of poorly managed pain
• Unable to wean off ventilator support
• Pulmonary dysfunction – atelectasis and pneumonia
-particularly after thoraco/abdominal surgery
- Decreased lung volumes, FRC, FCV
- Impaired cough reflex
Venous stasis and immobility – thrombus formation

6. Complications of inadequate pain management

7. How to assess pain in ICU
• Unable to communicate effectively
• Cognitive impairment
• Sedation
• Paralysis
• Mechanical ventilation

8. Signs of pain in ICU
• Hypertension
• Tachycardia
• Lacrimation
• Sweating
• Pupillary dilation
• Grunting

9. Behavioural pain scale (intubated patients)
• Score <3 no pain
• Score 4-5 mild
• Score 6-11 unacceptable pain
• Score >12 maximal pain

10. Critical-Care Pain Observation Tool

11. Principles of sedation and analgesia
• Consider individual patient characteristics when selecting analgesic
and sedative medications
• – Correct underlying conditions
• – Considering underlying metabolic/excretion capacities
• – Considering adverse effects of sedatives/Analgesics

12. Methods of drug administration
• Oral
• Intramuscular
• Intravenous
• Per rectal-suppositories
• Subcutaneous-patches
• Oral Transmucosal-lolly pops
• Inhalational
• Nasal spray
• Regional blocks
• Epidural

13. Opioids
• Opioids are the principal analgesics used in the ICUs
• 1.Potency,
• 2.Concomitant mild sedative
• 3.Anxiolytic properties
• 4. Change in sensorium, euphoria
• 5.Ability to be administered by multiple routes
• Morphine, fentanyl, hydromorphone

14. Side effects of opioids
• Respiration depression
• bradycardia
• constipation
• nausea, vomiting
• urinary retention
• Pruritus
• Withdrawal – 1/3 of all patients on opioids >1 week. Start weaning as
soon as tolerating

15. Morphine
• Most commonly used opioid
• Primarily metabolised by liver and renally excreted.
• Active metabolites of concern, morphine-3-glucuronide (M-3-G) and
morphine-6-gluconoride (M-6-G). Accumulation of M-6-G in those
with renal insufficiency can produce opioid toxicity and adverse
effects such as nausea, sedation, and respiratory depression.
• Accumulation of M-3-G may lead to myoclonus and seizures.
• Avoid morphine in renal failure
• Release of histamines produces allergic reaction and vasodilatation –
can lead to cardiac instability

16. Fentanyl
• Synthetic opioid 100 x potency of morphine
• More lipid soluable than morphine, CNS permeable producing
analgesia with 1/100 of morhines dose.
• Does not cause histamine response and vasodilatation
• Preferred drug in haemodynamically unstable patients
• Due to lipid soluability – administration >5days causes accumulation
in adipose tissues and prolonged sedation once opioid stopped

17. Hydromorphone (Jurnita)
• Semisynthetic opioid, 5-6 times more potent parenterally than
morphine
• Longer duration of action than fentanyl.
• Does not significantly accumulate in patients with renal failure and
thus may avoid neuroexcitability and cognitive impairment relative to
what is typically seen for those receiving morphine.

18. NSAID’s
• Salicylates-Aspirin
• Propionic acid derivatives-Ibuprofen
• Acetic acid derivatives-Indomethacin,Diclofenac,Ketorolac
• Oxicam derivatives-Piroxicam,Meloxicom
• Fenamic acid derivatives-Mefeamic acid
• Cox-2 inhibitors-Celecoxib,Valdecoxib
• Sulphonanilides-Nimmesulide
• Others-Licofelone

19. Non-steroidal anti-inflammatory drugs
(NSAIDS)
• Analgesic, antipyretic, anti-inflammatory actions
• Effective for headaches, dental, musculoskeletal pain including bone cancer
pain, yet not very effective or visceral pain (MI, acute abdomen)
• Prolonged NSAID use >2months –
• Risk of endoscopic ulcer is 1 in 5
• Symptomatic ulcer is 1 in 70
• Bleeding ulcer is 1 in 150
• Death from bleeding ulcer 1 in 1300
• Renal dysfunction
• Anti-platelet effect leading to blood loss

20. NSAID method of action
GI mucosa protection
Haemostasis
Mediates pain,
inflammation, fever

21. MOA
• NSAIDS all inhibit Cyclo-oxygenase (COX), also resulting in
prostaglandin synthesis inhibition
• COX1 exists in tissue as a constitutive isoform, but at inflammation
sites changed to COX2.
• Inhibition COX1 adds side effects for gastro-intestinal toxicity.
• Selective inhibition of COX2 responsible for anti-inflamatory
properties eg Celecoxib and Etoricoxib. Reduction of GIT side effects
by 50%.
• COX2 side effects – increased incidence of myocardial infarction and
strokes

22. Paracetamol

23. Paracetamol
• Central anti-nociceptive effect & potential mechanisms for this
include inhibition of a CNS COX-2
• Inhibition of a central cyclooxygenase ‘COX-3’ that is selectively
susceptible to paracetamol,
• Modulation of inhibitory descending serotinergic pathways
• Prevent PG production at the cellular transcriptional level,
independent of cyclooxygenase activity

24. Paracetamol Safety benefits
• No centrally mediated side-effects (e.g. sedation, constipation,
nausea, vomiting, respiratory depression)
• No effect on platelet aggregation, bleeding, or uric acid excretion
• No gastrointestinal side effects
• Good renal and hepatic safety (except in overdose)
• Few contra-indications and drug interactions

25. Local Anaesthetics
• Action—block the Na+ channels –impulse conduction
• Routes—oral, infiltration, spinal, epidural, sc patches, topical etc
• A major drawback analgesia treatment is tachyphylaxis
• Drugs—lignocaine,bupivicaine
• Toxic effects – CNS & CVS

26. Sedation

27. Goals of sedation
• Patient comfort
• Control of pain
• Anxiolysis and amnesia
• Blunting adverse autonomic and hemodynamic responses
• Facilitate nursing management
• Facilitate mechanical ventilation
• Avoid self extubation
• Reduce oxygen consumption

28. Assessment
• Anxious and agitated patients correct the following:
• Hypoxemia
• Hypoglycemia
• Hypotension
• Pain
• Alcohol withdrawal

29. Subjective methods of assessment of
sedation
• The Ramsay Scale
• The Glasgow Coma Scale modified by Cook and Palma, GCSC
• The Sedation Agitation Scale, SAS
• The Richmond Agitation and Sedation Scale, RASS
• The Bloomsbury sedation scale
• the Adaptation to the Intensive Care Environment (ATICE) scale
• The Avripas sedation scale
• the Comfort scale for pediatric patients.

30. GCSC, Glasgow Coma Scale modified by Cook
and Palma
• useful in mechanically ventilated patients
• Absence of agitation scoring
• Unuseful to monitor sedation in agitated patients
• Mechanical ventilation – 8-12, assisted volume control 8-12, Pressure controlled 8-12

31. Signs of inadequate sedation
Undersedated Oversedated
Agitation & anxiety
Pain and discomfort
Catheter displacement
Inadequate ventilation
Hypertension
Tachycardia
Arrhythmias
Myocardial ischemia
Wound disruption
Patient injury
Prolonged sedation
Delayed emergence
Respiratory depression
Hypotension
Bradycardia
Increased protein breakdown
Muscle atrophy
Venous stasis
Pressure injury
Loss of patient-staff interaction
Increased cost

32. Sedation Options: Benzodiazepines (Midazolam
and Lorazepam)
• Pharmacokinetics/dynamics
• Lorazepam: onset 5 - 10 minutes, half-life 10 hours, glucuronidated
• Midazolam: onset 1 - 2 minutes, half-life 3 hours, metabolized by
cytochrome P450, active metabolite (1-OH) accumulates in renal
disease
• Benefits – Anxiolytic, Amnestic, Sedating

33. Risks of benzodiazepines
• Delirium
• NO analgesia
• Excessive sedation: especially after long-term sustained use
• Propylene glycol toxicity (parenteral lorazepam): significance uncertain
• - Evaluate when a patient has unexplained acidosis
• - Particularly problematic in alcoholics (due to doses used) and renal
failure
• Respiratory failure (especially with concurrent opiate use)
• Withdrawal

34. Propofol
• Pharmacology: GABA agonist
• Pharmacokinetics/dynamics: onset 1 - 2 minutes, terminal half-life 6
hours, duration 10 minutes, hepatic metabolism
• Benefits
- Rapid onset and offset and easily titrated
- Hypnotic and antiemetic
- Can be used for intractable seizures and elevated intracranial pressure
• Dosing - 3-5 ug/kg/min antiemetic, 5-20 ug/kg/min anxiolytic, 20-50
ug/kg/min sedative hypnotic, >100 ug/kg/min anesthetic

35. Risks of Propofol
• Not reliably amnestic, especially at low doses
• NO analgesia!
• Hypotension
• Hypertriglyceridemia; lipid source (1.1 kcal/ml)
• Respiratory depression
• Propofol Infusion Syndrome
• - Cardiac failure, rhabdomyolysis, severe metabolic acidosis, and renal
failure
• - Caution should be exercised at doses > 80 mcg/kg/min for more than
48 hours
• - Particularly problematic when used simultaneously in patient
receiving catecholamines and/or steroids

36. Barbiturates
• Infusion doses are subhypnotic
• Thiopental: 1-5 mg/min
• Methohexital: 0.5-2.5 mg/min
• Prolonged infusion of methohexital is associated with a more rapid
recovery than thiopental because the clearance rate of methohexital
is 3-4x’s higher, resulting in a shorter elimination half-life

37. Ketamine
• Low dose infusions (5-25 mcg/kg/min) effective for sedation in the
ICU and for local or regional anesthetic procedures
• Significantly decreases the opioid analgesic requirement when used
for ICU sedation
• Effective for burn care

38. Task Force of the American College of Critical Care
Medicine - 1995
• Recommendations:
• Sedation
Midazolam and propofol for short term (<24 hours)
Lorazepam for long term
• Analgesia
Morphine for most patients
Fentanyl for hemodynamically unstable patients

43. Non-pharmacological treatment of pain
• Proper positioning and regular position changes
• Stabilise fractures
• Avoid traction of ETT/ NGT/ catheters/ lines
• Superficial heat – heat effects 1-2cm from skin surface. Deminishes pain and
decreases local muscle spasm
• Cryotherapy – reduce intramusucular temperatures between 3-7C, reduces local
metabolism, inflammation, pain, local nerve conduction velocity causing cold-
induced neuropraxia
• Percutaneuous electrical nerve stimulation PENS, relieve symptoms in peripheral
neuropathy
• Acupuncture – releases endorphins, increases flow of oxygen and blood to area
• Physiotherapy

44. References
• Barr et al. Clinical Practice Guidelines for the Management of Pain,
Agitation, and Delirium in Adult Patients in the Intensive Care Unit
2013
• Neal et al – Medical Pharmacology 6th Edition p65-68
• Griggs et al. Sedation and Pain management in burns patients.
Journal of clinical plastic surgery. 2017 44(3)