2. Pain: Why treat it? Humanitarian JCAHO (2001)
Blunt autonomic and somatic response to pain
- Elevated metabolic rate
- Elevated O2 consumption
- Hypercoagulability
- Altered immune status
- Development of chronic pain

3. Pain: Why Don’t We Treat It Well?
Lack of concern/caring
Lack of knowledge
Uniform prescribing practices
Fear of side effects
Fear of addiction

4. Armamentarium Guided imagery (!) Patient education Narcotics NSAIDs
Gaba agonists
Local/regional anesthetics
“Preemptive” treatment
“Procedure specific” – Prospect website

5. Local anesthetics
Dose-dependent blockage of sodium channels in neurons
Amides and esters (amides less allergenic)
Amides:Lidocaine, bupivacaine, prilocaine
Esters: Novocaine
Lidocaine dosing: 5 mg/kg without epi
7 mg with epi

6. NSAIDS Conventional Cox inhibitors Cox 2 inhibitors
Decreased incidence of GI bleeding
Didn’t inhibit platelet aggregation
Initial data on side effects was on usage for greater than 1-2 years
Now some data on side effects as analgesics for CABG patients

7. Gabapentin/Pregabalin
How do they work?
Who knows?
Presynaptic binding to calcium channels in brain
Decrease excitatory transmission

8. Narcotics Morphine Fentanyl Hydromorphone All work on mu receptors
Decrease responsiveness of resp center to CO2
Stimulate medullary chemoreceptor trigger zone
Increase sphincter tone and decrease peristalsis

9. Opiate Analgesic Options: Fentanyl, Morphine, Hydromorphone
Rapid onset X
Rapid offset X*
Avoid in renal disease
X**
Preload reduction
Avoid in hemodynamic instability
Equivalent doses
100 mcg
1.5 mg
10 mg
* Offset prolonged after long-term use
** Active metabolite accumulation causes excessive narcosis

10. Rescue/Bolus Doses
MSO mg-0.3 mg/kg IV (70 kg – 7-21 mg IV!!!) – I give 5
Fentanyl mg IV
Dilaudid mg/kg IV (70 kg – mg IV)

11. PCA
MSO4
Dose 1.5 mg
Lockout 7 min
4 hr limit 30
How do you adjust?

12. PCA Fentanyl Dose 20 mcg Lockout 7 min 4 hour dose 300 mcg
When do you use it?

13. PCA
Dilaudid
Dose 0.2 mg
Lockout 7 mg
4 hr limit 3 mg

14. Case 1
36 y.o morbidly obese woman with RUQ pain at 20 hrs, RUQ tenderness, WBC 13, US with stones, wall 5.0 mm
What’s she got?
How will we manage her pain? What are our Prospects?

15. Case 1

16. Case 2 65 y.o. man with COPD here for esophageal cancer
What operation is he going to get?

18. Epidural Anesthesia What is good about it? Decreases risk of DVT
Increases risk of graft thrombosis
Decreases post op ileus in upper abd surgy
Decrease ICU days and vent days after abd vasc surgery

19. Flavors of epidurals Narcotics Narcotics + Local anesthetics
Complications:
Rostrol migration of morphine with respiratory depression up to 18 hrs after
Hypotension from sympathectomy

20. P.O. Conversion
Morphine 10 mg. = oxycodone 20 mg

21. Case 3
20 y.o. man MCC intubated in field for combativeness, open femur, SAH and L cerebral contusion, etoh 498
What’s going to happen to him tonight?

22. Case 3 Back from the OR Ex-fix, EVD with ICP 16
What meds will you write for? What do you have to treat?

23. Sedation Options: Propofol
Pharmacology: GABA agonist
Pharmacokinetics/dynamics: onset 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
Risks
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

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

25. Case 3 Continuous infusion Fentanyl 1 mcg/kg/hr MS04 1-5 mg/hr
Midazolam 1-4 mg/hr
Lorazepam 1-4 mg/hr
Propofol – mcg/kg/min (packaged at 10mg/cc; approx cc/hr for 70 kg pt)

26. Overview of SCCM Algorithm1 2 3 4
Jacobi J, Fraser GL, Coursin D, et al. Crit Care Med. 2002;30:

27. Overdose
Nalaxone
flumazenil

29. Address Pain

30. Atypical Antipsychotics: Quetiapine, Olanzapine, Risperidone, Ziprasidone
Mechanism of action unknown
Less movement disorders than haloperidol
Enhanced effects on both positive (agitation) and negative (quiet) symptoms
Efficacy = haloperidol?
One prospective randomized study showing equal efficacy of olanzapine to haldol with less EPS
Issues
Lack of available IV formulation
Troublesome reports of CVAs, hyperglycemia, NMS
Titratability hampered
- QTc prolongation with ziprasidone IM
- Hypotension with olanzapine IM

31. Haloperidol
No prospective randomized controlled trials in ICU delirium
> 700 published reports involving > 2,000 patients
The good:
Hemodynamic neutrality
No effect on respiratory drive
The bad:
QTc prolongation and torsades de pointes
Neuoroleptic malignant syndrome - only three cases with IV haloperidol
Extrapyramidal side effects - less common with IV than oral haloperidol

33. Opiate and Benzodiazepine Withdrawal
Frequency related to dose and duration
32% if receiving high doses for longer than a week
Onset depends on the half-lives of the parent drug and its active metabolites
Clinical signs and symptoms are common among agents
CNS activation: seizures, hallucinations,
GI disturbances: nausea, vomiting, diarrhea
Sympathetic hyperactivity: tachycardia, hypertension, tachypnea, sweating, fever
No prospectively evaluated weaning protocols available
% daily decrease in dose
% initial decrease in dose with additional daily reductions of %
Consider conversion to longer acting agent or transdermal delivery form

34. Protocols and Assessment Tools
SCCM practice guidelines can be used as a template for institution-specific protocols.
Titration of sedatives and analgesics guided by assessment tools:
Validated sedation assessment tools (Ramsay Sedation Scale [RSS], Sedation-Agitation Scale [SAS], Richmond Sedation-agitation Scale [RSAS], etc.)
- No evidence that one is preferred over another
Pain assessment tools - none validated in ICU (numeric rating scale [NRS], visual analogue scale [VAS], etc.)

35. Daily Goal is Arousable, Comfortable Sedation
Sedation needs to be protocolized and titrated to goal:
Lighten sedation to appropriate wakefulness daily.
Effect of this strategy on outcomes:
One- to seven-day reduction in length of sedation and mechanical ventilation needs
50% reduction in tracheostomies
Three-fold reduction in the need for diagnostic evaluation of CNS

36. Appropriate Recall May be Important
Factual memories (even unpleasant ones) help to put ICU experience into perspective
Delusional memories risk panic attacks and PTSD
The optimal level of sedation for most patients is that which offers comfort while allowing for interaction with the environment.

37. Recall in the ICU
Some degree of recall occurs in up to 70% of ICU patients.
Anxiety, fear, pain, panic, agony, or nightmares reported in 90% of those who did have recall.
Potentially cruel:
Up to 36% recalled some aspect of paralysis.
Associated with PTSD in ARDS?
41% risk of recall of two or more traumatic experiences.
Associated with PTSD in cardiac surgery

38. What We Know About ICU Agitation/Discomfort
Prevalence
50% incidence in those with length of stay > 24 hours
Primary causes: unrelieved pain, delirium, anxiety, sleep deprivation, etc.
Immediate sequelae:
Patient-ventilator dyssynchrony
Increased oxygen consumption
Self (and health care provider) injury
Family anxiety
Long-term sequelae: chronic anxiety disorders and post-traumatic stress disorder (PTSD)

39. Opiates Benefits Risks
Relieve pain or the sensibility to noxious stimuli
Sedation trending toward a change in sensorium, especially with more lipid soluble forms including morphine and hydromorphone.
Risks
Respiratory depression
NO amnesia
Pruritus
Ileus
Urinary retention
Histamine release causing venodilation predominantly from morphine
Morphine metabolites which accumulate in renal failure can be analgesic and anti-analgesic.
Meperidine should be avoided due to neurotoxic metabolites which accumulate, especially in renal failure, but also produces more sensorium changes and less analgesia than other opioids.