Pharm III Week 8 (Acute Pain and Anesthesia)

Preoperative evaluation

Anxiolytics

Antisialogogues

Antiemetics

Anesthetic Induction

IV Anesthetics

Opioids

Intraoperative Management

Inhaled Anesthetics

Neuromuscular Blockers

Local/Regional Anesthetics

Opioids

Recovery (PACU)

Reversal Agents

Antiemetics

Analgesics

Postoperative Pain Management

Non-opioid Analgesics

Opioids

Adjunctive Analgesics

Poorly controlled acute pain is associated with:

- Increased postoperative complications

- Delayed mobilization

- Longer hospital stays

- Higher risk of developing chronic postsurgical pain

Multimodal analgesia reduces ________ requirements while improving pain control and recovery

Multimodal analgesia reduces opioid requirements while improving pain control and recovery

An average surgical patient receives multiple medication classes in just a few hours

Goals of Anesthesia

• Analgesia: Pain Control

• Hypnosis: Unconsciousness

• Amnesia: No memory

• Immobility: Muscle relaxation

• Physiologic Stability: Maintain oxygenation and hemodynamics

pain signaling pathway

Step 1: Tissue Injury (30 seconds)

med class blocks this inflammatory response? → NSAIDs

Step 2: Transduction --> nociceptors

Drugs: NSAIDs, APAP, Corticosteroids

Step 3: Transmission

Step 4: Modulation

Endogenous opioids, serotonin, Norepi

Step 5: Perception (signal reaches higher brain centers)

Multimodal Approach to Pain with Pain Pathway

Multimodal analgesia

Combining medications with different mechanisms of action to improve pain control that target multiple points along the pain pathway while minimizing opioid-related adverse effects

Foundation Meds for Analgesia

Foundation (Almost Every Patient)

•Acetaminophen

•NSAIDs (if appropriate)

Procedure-Specific Meds for Analgesia

•Local anesthetic infiltration

•Peripheral nerve block

•Epidural/spinal anesthesia

Breakthrough or Moderate-Severe Pain

Opioids (morphine, hydromorphone, fentanyl, oxycodone)

Adjunct Agents / Specific Situations

•Ketamine

•Dexmedetomidine

•Gabapentinoids

Non-opioid Analgesics: First-line therapy - Acetaminophen

MOA *KNOW*

- Central analgesic and antipyretic

- Inhibits central prostaglandin synthesis (primarily COX activity within the CNS)

- Minimal peripheral anti-inflammatory activity

APAP Clinical Uses

*KNOW*

Mild to moderate acute pain

Fever reduction

Opioid-sparing agent

APAP Advantages

*KNOW*

Multiple formulations (PO, rectal, IV)

Minimal gastrointestinal irritation

No effect on platelet function

Safe in patients with bleeding risk or PUD

APAP Limitations & Adverse Effects

*KNOW*

Generally well tolerated at therapeutic doses

Hepatotoxicity with overdose or chronic excessive dosing

Use caution in (consider limiting dosage):

- Significant hepatic impairment

- Chronic alcohol use

- Malnutrition

Non-opioid Analgesics: First-line therapy

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and MOA

Reversibly inhibit cyclooxygenase (COX-1 and/or COX-2)

↓ Prostaglandin synthesis

Produce analgesic, antipyretic, and anti-inflammatory effects

NSAIDs - COX-1

role? if inhibited?

*KNOW*

"Housekeeping" Enzyme

- Gastric protection

- Platelets

- Kidney perfusion

If Inhibited:

- GI Bleeding

- Bleeding Risk

- AKI

NSAIDs - COX-2

role? if inhibited?

*KNOW*

"Inflammation" Enzyme

- Triggers inflammation

- Creates pain

-Generates fever

If Inhibited:

- Analgesia

- Anti-inflammatory

- Antipyretic

Non-opioid Analgesics: First-line therapy

COMMONLY USED NSAIDS

NSAIDS - Avoid / Use Caution

*KNOW*

Active GI bleeding or peptic ulcer disease

Significant renal dysfunction or AKI

NSAID hypersensitivity/AERD

Late pregnancy

Severe heart failure

*Ketorolac monitor length of time (

NSAIDs Major Adverse Effects

GI ulceration and bleeding

Acute kidney injury

Platelet inhibition (nonselective NSAIDs)

Fluid retention and hypertension

Cardiovascular thrombotic risk (COX-2 selective agents)

NSAID Clinical Pearls

- Use lowest effective dose for shortest duration; avoid concurrent NSAIDs

- Ketorolac: limit to ≤5 days (GI/renal toxicity)

- Monitor renal function in high-risk patients

Non-opioid Analgesics (topicals)

Lidocaine, Diclofenac, Capsaicin

Lidocaine (Local anesthetic) use

- Localized or superficial pain

- Topical patch, cream, gel

- Useful for localized neuropathic pain

- Minimal systemic effects when used appropriately

Diclofenac (Topical NSAID) use

- Localized MSK/inflammatory pain

- Lower systemic exposure than oral NSAIDs

- Useful for minor injuries and osteoarthritis

- Still consider NSAID-related precautions

Capsaicin (TRPV1 agonist) use

- Primarily neuropathic pain

- More commonly used for chronic pain

- Initial burning/irritation is common

- Limited role in acute postoperative pain

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Overview

• Significant risk of tolerance, dependence, and misuse

• No universal maximum analgesic dose ... No true analgesic ceiling! Higher doses can provide greater analgesia, but toxicity increases

•Dose should be individualized and titrated to effect

•Use the lowest effective dose for the shortest appropriate duration

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Adverse effect profile: COMMON

Sedation / drowsiness

N/V

Constipation

Pruritus

Dizziness

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Adverse effect profile: DOSE LIMITING/SERIOUS

- Respiratory depression

- Hypotension

- Bradycardia

- Urinary retention

- Delirium / altered mental status

- Chest wall rigidity (IV fentanyl)

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Adverse effect profile: W/ REPEATED OR PROLONGED USE

- Tolerance

- Physical dependence

- Opioid-induced hyperalgesia

- Misuse / opioid use disorder

OPIOIDS - Risk increases with?

Risk increases with: higher doses, rapid IV administration, opioid-naïve patients, and concurrent CNS depressants (e.g., benzodiazepines, alcohol)

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Managing Adverse Effects - Respiratory Depression

*KNOW*

First-Line Intervention: Decrease/hold opioid; support ventilation

Alternative / Adjunctive Intervention: Naloxone if clinically significant; possibly nalbuphine

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Managing Adverse Effects - N/V

*KNOW*

First-Line Intervention: Antiemetic agent

Alternative / Adjunctive Intervention: Dose reduction/opioid rotation; motility agents such as metoclopramide in selected patients

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Managing Adverse Effects - Constipation

*KNOW*

First-Line Intervention: Stimulant laxative ± stool softener

Alternative / Adjunctive Intervention: Osmotic laxative; opioid rotation

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Managing Adverse Effects - Pruritus

*KNOW*

First-Line Intervention: Decrease dose or switch opioid

Alternative / Adjunctive Intervention: Antihistamine; low-dose naloxone/nalbuphine

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Managing Adverse Effects - Hypotension

*KNOW*

First-Line Intervention: Decrease/hold opioid; supportive care

Alternative / Adjunctive Intervention: Fluid resuscitation/vasopressor if clinically indicated

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Managing Adverse Effects - Tolerance

*KNOW*

First-Line Intervention: Reassess pain; optimize multimodal analgesia

Alternative / Adjunctive Intervention: Opioid rotation; non-opioid analgesic

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Managing Adverse Effects - Withdrawal

*KNOW*

First-Line Intervention: Re-evaluate/slow weaning regimen

Alternative / Adjunctive Intervention: Rescue dosing, add another agent such as clonidine; longer-acting opioid when appropriate

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Common IV formulations: MORPHINE

Onset

Duration

Potency

Hemodynamics

Histamine Release

Active Metabolites

Clinical Considerations

*KNOW*

Morphine

onset ~5-10 min

duration 3-5 hr

potency 1x

↓ BP possible

More histamine release

Yes active metabolites

Renal dysfunction matters

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Common IV formulations: HYDROMORPHONE

Onset

Duration

Potency

Hemodynamics

Histamine Release

Active Metabolites

Clinical Considerations

*KNOW*

Hydromorphone

onset ~5 min

duration 3-4 hr

potency ~ 5-7 × morphine

↓ BP possible

Less histamine release

Yes active metabolites (less than morphine)

Dosing errors can be significant

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Common IV formulations: FENTANYL

Onset

Duration

Potency

Hemodynamics

Histamine Release

Active Metabolites

Clinical Considerations

*KNOW*

Fentanyl

onset ~1-2 min (RAPID)

duration 30-60 min (SHORTEST)

potency ~ 50-100× morphine

Minimal effect on BP

Minimal histamine release

No clinically significant active metabolites

Rapid IV administration could cause chest wall rigidity; dosed in mcg versus mg

pearl for dosing for opioids

Start with intermittent opioid dosing (scheduled and/or PRN) and reassess frequently

for persistent or severe pain requiring frequent rescue doses, consider escalation to continuous infusion and/or PCA when appropriate

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Common ORAL Options and Considerations

Oxycodone IR: common option for acute moderate-severe pain

Hydrocodone/APAP: frequently used for acute pain; monitor total APAP exposure

Morphine IR: option for moderate-severe pain; renal function matters

Hydromorphone IR: highly potent; typically reserved for more severe pain or when other opioids are unsuitable

Codeine: variable metabolism and analgesic response; generally not preferred

Why avoid ER opioids for routine acute pain?

do not use

Slow onset: poor fit for rapidly changing pain

Long duration: difficult to titrate

Accumulation: prolonged adverse effects

Higher risk: especially in opioid-naïve patients

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Methadone

*KNOW*

Methadone (PO/IV)

- Selected perioperative use; long duration

- May be useful in opioid-tolerant patients

- Long, variable half-life → accumulation

- QT prolongation + significant drug interactions (CYP-mediated)

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Tramadol

Tramadol (PO)

- Mild-moderate acute pain

- Variable analgesic response (CYP2D6)

- Seizures + serotonin syndrome

- Generally not preferred over conventional short-acting opioids when an opioid is indicated

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Nalbuphine (IV/IM/SubQ)

*KNOW*

Nalbuphine (IV/IM/SubQ)

- Opioid-induced pruritus

- κ-agonist / μ-antagonist → may precipitate withdrawal or reduce analgesia

- Ceiling effect on respiratory depression (may have less severe respiratory depression)

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Butorphanol (IV/IM/IN)

Butorphanol (IV/IM/IN)

- Alternative for acute moderate-severe pain

- κ-agonist / μ-partial agonist-antagonist

- Less commonly used than traditional full μ-agonists

- IN formulation: alternative/rescue therapy for migraine

- May precipitate withdrawal

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Meperidine (IV/IM)

Meperidine (IV/IM)

- Limited role in acute pain

- More commonly encountered for postoperative shivering

- Normeperidine accumulation leading to neurotoxicity/seizures

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Escalating therapy - intermittent dosing

Intermittent Dosing: Scheduled and/or PRN PO or IV opioids

- Reassess, Is pain adequately controlled? How often are rescue doses needed? Is the patient experiencing sedation or other toxicity? Is the current route appropriate? Is multimodal analgesia optimized?

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Escalating therapy - When to escalate? Consider Alt delivery such as?

Escalate When:

- Frequent rescue doses are required

- Pain is persistent or predictable

- Intermittent dosing provides inadequate duration of relief

- Opioid requirements are high or difficult to predict

- Patient cannot reliably tolerate/use the PO route

Consider Alternative Delivery

- Continuous Infusion

- Patient-Controlled Analgesia

Opioid Analgesics: Breakthrough or Mod-Severe Pain

Patient Controlled Analgesia (PCA)

Patient can push a button and receive medication dose via IV

Can be useful in patients with post-op pain who are extubated; allows autonomy

Common medications: fentanyl, morphine, hydromorphone

Opioid Analgesics: Breakthrough or Mod-Severe Pain

CNCA = Caregiver/Nurse Controlled Analgesia

An authorized operator to administer pain medication to the patient

A nurse must generally complete education relating to CNCA utilization

Usage will be covered with the caregiver prior to initiation of CNCA

Consideration for use: patients who are developmentally, cognitively, or physically unable to understand or operate the pump

Opioid Analgesics: Breakthrough or Mod-Severe Pain - Parameters Included

Basal rate

Bolus amount

Lockout interval

4-hour maximum dose

Case #1

42-year-old patient is recovering in the PACU after an open abdominal surgery. Before surgery, the patient received scheduled acetaminophen and ketorolac as part of a multimodal analgesic regimen.

Thirty minutes after arrival in the PACU, the patient reports 8/10 incisional pain and says, "The pain is getting worse when I try to take a deep breath."

The patient has no history of chronic opioid use and has not received an opioid since surgery. Vitals stable.

What is the most appropriate next step?

A. Give another dose of acetaminophen

B. Administer an opioid for breakthrough pain

C. Administer midazolam for anxiety

D. Withhold analgesia because the patient is hemodynamically stable

B. Administer an opioid for breakthrough pain

Case #1

The provider is considering fentanyl vs. morphine for IV rescue analgesia.

Which characteristic would favor fentanyl in this PACU patient?

A.Longer duration of action

B.Greater oral bioavailability

C.Rapid onset of analgesia

D.Lack of respiratory depression

C.Rapid onset of analgesia

Adjunct Agents: select cases

Overview - When Might We Add An Adjunct?

*KNOW*

- Pain inadequately controlled with standard therapy

- Opioid-sparing is desirable

- High opioid requirements or opioid tolerance

- Specific pain mechanism (e.g., neuropathic pain)

- Need for additional analgesia without simply increasing opioid dose

Ketamine: MOA

NMDA receptor antagonist

Reduces central sensitization and nociceptive signaling

Produces analgesia at subanesthetic doses (higher dosing for anesthesia)

Ketamine

Role in Acute Pain (IV, IM, IN PO (off-label/compounded))

Opioid-sparing strategy

Moderate-severe acute pain, particularly when conventional analgesia is inadequate

May be useful in opioid-tolerant patients

Can reduce opioid requirements

IV administration allows titration in monitored settings

Ketamine: Key Adverse Effects *KNOW*

Increased HR / BP

Increased secretions

Sedation

Nausea/vomiting

Dysphoria, hallucinations, emergence reactions

Adjunct Agents

α₂-Adrenergic Agonists

dexmedetomidine

clonidine

α₂-Adrenergic Agonists MOA

Stimulate central α₂-adrenergic receptors

↓ norepinephrine release and ↓ sympathetic activity

Produces sedation and analgesic-sparing effects

α₂-Adrenergic Agonists Role in Acute Pain (IV, PO)

Opioid-sparing adjunct

Perioperative and procedural analgesia (where sedation is also desirable)

Can reduce opioid requirements

Dexmedetomidine: commonly used IV in monitored settings

Clonidine: enteral agent; may be used as an adjunct and can help manage opioid withdrawal symptoms

α₂-Adrenergic Agonists: Key Adverse Effects

Bradycardia

Hypotension

Sedation

Dry mouth

Possible rebound hypertension with abrupt clonidine discontinuation

Adjunct Agents: Gabapentinoids (GABAPENTIN, PREGABALIN)

MOA

Bind the α₂δ subunit of voltage-gated calcium channels

↓ excitatory neurotransmitter release

Reduce neuronal hyperexcitability

Gabapentinoids (GABAPENTIN, PREGABALIN)

Role in Acute Pain (PO)

Primarily useful when neuropathic pain is present

May be used as part of multimodal perioperative analgesia

Can reduce opioid requirements

Not typically first-line for routine acute nociceptive pain

Pregabalin > gabapentin in terms of predictable absorption and simpler dosing

Gabapentinoids (GABAPENTIN, PREGABALIN)

Key Adverse Effects

Sedation

Dizziness

Ataxia

Peripheral edema

Respiratory depression risk when combined with opioids/CNS depressants

Case 1: 42 y/o pt recovering in PACU after an open abd surgery. Before surgery, pt received acetaminophen and ketorolac as part of a multimodal analgesic regimen.

30 min after arrival in the PACU, pt reports 8/10 incisional pain and says, "The pain is getting worse when I try to take a deep breath." pt has no history of chronic opioid use and has not received an opioid since surgery.

After receiving IV fentanyl, the patient's pain decreases to 3/10. The provider wants to minimize additional opioid requirements.

Which strategy best represents multimodal analgesia?

A. Continue escalating the opioid until pain is completely eliminated

B. Use medications with different mechanisms to reduce opioid requirements

C. Avoid non-opioid analgesics once an opioid is started

D. Use a benzodiazepine to enhance opioid analgesia

B. Use medications with different mechanisms to reduce opioid requirements

CASE 1

Several hours later, the patient becomes increasingly somnolent. RR is 7/min, SpO₂ is 86%, and the patient is difficult to arouse.

What is the most appropriate initial priority?

A.Administer another dose of fentanyl

B.Administer flumazenil

C.Administer ketorolac

D.Support airway/ventilation and administer naloxone as appropriate

D. Support airway/ventilation and administer naloxone as appropriate

Stages of Anesthesia

Induction

•Initiate anesthesia → loss of consciousness

•Establish/protect airway

•Sedate before you paralyze (bc paralytics = NO analgesic effect)

Maintenance

•Maintain appropriate depth of anesthesia

•Balance hypnosis, analgesia & immobility

•Monitor/support vital functions

Recovery / Emergence

•Reduce/discontinue anesthetic agents

•Return of consciousness & protective reflexes

•Manage airway and pain

depth of anesthesia: too light vs too deep?

Too light: awareness, movement, physiologic response

Too deep: hypotension, respiratory depression, delayed emergence

Types of Anesthesia

General Anesthesia

Regional Anesthesia

Local Anesthesia

MAC / Sedation

general anesthesia

scope, consciousness, uses

Whole body / systemic

Unconscious

uses: Major abdominal surgery; thoracic surgery; intracranial surgery; procedures requiring airway control or complete immobility

regional anesthesia

scope, consciousness, uses

Large body region

Usually conscious

Cesarean delivery; total knee/hip arthroplasty; upper/lower extremity surgery; labor analgesia

local anesthesia

scope, consciousness, uses

Small, localized area

Conscious

Dental procedures; laceration repair; skin biopsy/excision; incision & drainage

Monitored Anesthesia Care/Sedation

scope, consciousness, uses

Varies

Sedation varies

Endoscopy/colonoscopy; bronchoscopy; cardiac catheterization; minor procedures requiring anxiolysis and/or sedation

LOCAL vs REGIONAL Anesthesia

Block the pain pathway before it reaches the brain

Local and regional anesthesia use the same local anesthetic drugs and mechanism; the difference is the site and extent of nerve blockade

Local and regional anesthesia use the same local anesthetic drugs and mechanism; the difference is the site and extent of nerve blockade

mechanism?

Peripheral nerve --> Na⁺ channel blockade --> No action potential --> No pain signal

Esters vs Amides

we like AMIDES!

esters

1) Plasma cholinesterase metabolism

2) PABA metabolite --> greater allergy potential

3) Less commonly used

examples of esters

•Procaine (not used anymore)

•Chloroprocaine

•Tetracaine

Amides

*KNOW*

1) Hepatic metabolism

2) Allergic reactions are rare

3) Most used

examples of amides

•Lidocaine ± epinephrine

•Mepivacaine

•Bupivacaine

•Articaine

Compare/Contrast Duration, Common Uses, and Considerations for these local and regional agents:

Lidocaine

Articaine

Bupivacaine

Ropivacaine

Mepivacaine

Anesthesia: Epinephrine Combined with Local Anesthetics

what does it do?

*KNOW*

•Vasoconstriction at injection site

•↓ systemic absorption

•↑ duration of local anesthesia

•↓ peak plasma concentration

•↓ local bleeding

Anesthesia: Epinephrine Combined with Local Anesthetics

Clinical Considerations

*KNOW*

1. Useful when prolonged anesthesia and/or hemostasis is desired

2. Consider injection site and patient factors

3. Use caution when significant vasoconstriction may be undesirable (ears, nose, fingers, toes - end arterial fields)

don't use with uncontrolled HTN, CHF

Anesthesia: Local Anesthetic Systemic Toxicity (LAST)

Cause

Excessive dose, rapid absorption, or inadvertent intravascular injection

Risk increases with highly potent/long-acting agents, particularly bupivacaine

Anesthesia: Local Anesthetic Systemic Toxicity (LAST)

CNS toxicity (early) results in

Perioral numbness/tingling

Metallic taste

Tinnitus

Dizziness/agitation

Seizures

Anesthesia: Local Anesthetic Systemic Toxicity (LAST)

CV toxicity (severe)

Hypotension

Conduction abnormalities

Ventricular arrhythmias

Cardiovascular collapse

Anesthesia: Local Anesthetic Systemic Toxicity (LAST)

Management

- Stop local anesthetic

- Support airway, breathing, circulation

- Treat seizures

- 20% lipid emulsion therapy for significant LAST (deactivates)

CASE #2: A 28 y/o otherwise healthy pt presents to the ED after sustaining a 5-cm laceration to the volar forearm from broken glass approximately 1 hour ago.

• The wound is irrigated and evaluated. There is no evidence of tendon, nerve, or vascular injury, and the patient has normal distal pulses and sensation.

• The patient is anxious but cooperative and reports 7/10 pain.

• The clinician plans to perform local infiltration before wound closure.

Which local anesthetic would be the most appropriate choice for this procedure?

A. Lidocaine

B. Bupivacaine

C. Tetracaine

D. Procaine

A. Lidocaine

CASE #2

The clinician is deciding between lidocaine and bupivacaine. The patient asks whether there is an option that would provide numbness for several hours after the procedure.

Which consideration would favor bupivacaine over lidocaine?

A. Faster onset

B. Longer duration of local anesthesia

C. Lower risk of cardiotoxicity

D. Greater effectiveness for short superficial procedures

B. Longer duration of local anesthesia

CASE #2

The clinician chooses lidocaine with epinephrine for the procedure. During the injection, the patient asks why epinephrine is being included.

Which effect of epinephrine best explains its use with a local anesthetic?

A. Directly increases the potency of the local anesthetic

B. Produces vasoconstriction, slowing systemic absorption of the local anesthetic

C. Prevents sodium-channel blockade

D. Provides additional local anesthesia through nicotinic receptor blockade

B. Produces vasoconstriction, slowing systemic absorption of the local anesthetic

Anesthesia Preoperative medications: Why do we give these?

•Reduce anxiety (benzos)

•Provide analgesia (opioids)

•Reduce airway secretions (anticholinergics/antisialogues)

•Prevent/treat post operative nausea and vomiting (antiemetics)

•Facilitate a smoother induction and recovery (Agent/Procedure Dependent)

Anesthesia Preoperative medications: Anxiolysis & Amnesia

agents?

LORAZEPAM

MIDAZOLAM (fav)

DIAZEPAM

MIDAZOLAM - more on why it is preferred compared to lorazepam and diazepam

*KNOW*

Rapid onset

Shorter duration than lorazepam/diazepam

- short half-life

- less prolonged postoperative sedation

No clinically relevant active metabolites

Predictable titration: IV doses can be given incrementally to achieve the desired effect

Anterograde amnesia: Useful before procedures

Multiple routes: IV, IM, oral, and intranasal formulations available

Reversible with flumazenil if clinically necessary