CASE MANAGEMENT

Respiratory Depression
after Spinal Anesthesia
 VISION

To become a premier department of Anesthesiology

in Bicol with the highest standard of anesthesia care.
 MISSION

To continue to provide safe anesthesia care through

training and research and to produce competent
diplomates in anesthesia who embody BMC core values.
Objectives
To define epidural and intrathecal
1 administration of opioids

To enumerate factors increasing the

2 risk of respiratory depression after
neuraxial anesthesia

To explain other complications of adding

3 drug adjuncts to neuraxial anesthesia

To discuss preventive measures to

4 minimize adverse outcomes of
respiratory depression from neuraxial
opioid analgesia
 • 78-year-old patient
CASE • Partial hip replacement surgery
• Under spinal anesthesia with 0.5%
bupivacaine and 0.1 mg of morphine
• Later that evening, she appears extremely
sleepy with O2 sat of 92% on nasal cannula
Respiratory changes after
neuraxial anesthesia

Blockade of Decrease in Decrease in vital Compensated by

intercostal and expiratory reserve capacity unaltered function
abdominal volume of diaphragm and
muscles accessory muscles

Miller's Anesthesia 8E (2015) p. 1690

 Neuraxial
refers to the epidural or spinal
administration of opioids, including
opioid
single injection, continuous or
intermittent infusion, and
analgesia
patient-controlled analgesia

Practice guidelines for the prevention, detection, and Management of Respiratory Depression
Associated with Neuraxial Opioid Administration: an updated report (2017)
 Neuraxial
better postoperative analgesia,
increased functional ability,
opioid
earlier ambulation and earlier
return of bowel function analgesia
negligible motor, sensory or
autonomic blockade
Practice guidelines for the prevention, detection, and Management of Respiratory Depression
Associated with Neuraxial Opioid Administration: an updated report (2017)
 3

Mechanism of action of opioids

Opioids exert its effects at receptors at all levels of the three-neuron system

Charuwattanapanit, I. (2020). Neuraxial Morphine: A review of Mechanism of Action and Respiratory

Depression. Thai Journal of Anesthesiology, 46(4), 245-260.
 Side effects
of opioid
Side effects of Opioid Medications: Calgary Guide (2015)
https://calgaryguide.ucalgary.ca/Side-Effects-of-Opioid-Medications/
 RESPIRATORY DEPRESSION

1 2 3
reduced respiratory reduced oxygen hypercapnia/
rate (<10 breaths/min) saturation (<90%) hypercarbia
(arterial CO2 tension
>50 mmHg)
Other measures: tidal volume, clinical signs (drowsiness, sedation, periodic apnea, cyanosis)
Practice guidelines for the prevention, detection, and Management of Respiratory Depression
Associated with Neuraxial Opioid Administration: an updated report (2017)
2 3 factors combine to decrease
ventilation, reduce pulmonary gas
exchange resulting in hypoxia and
hypercapnia
1. Depression of respiratory drive
1 2. Depression of consciousness
3. Depression of supraglottic
airway muscle tone

3 Mechanism of
respiratory depression
associated with
neuraxial opioids

Charuwattanapanit, I. (2020). Neuraxial Morphine: A review of Mechanism of Action and Respiratory

Depression. Thai Journal of Anesthesiology, 46(4), 245-260.
 <1% risk after intrathecal or
epidural opioid
Respiratory Data suggests risk is similar to parenteral opioids

depression Biphasic w ith early and

after delayed presentations

neuraxial Delayed presentation associated with hydrophilic

opioids (morphine, hydromorphone)

opioids Delayed respiratory depression occurs

6-12 hours after administration
Can persist up to 24 hours

Bujedo, B. M. (2013). Recommendations for spinal opioids clinical practice in the

management of postoperative pain. J Anesthesiol Clin Sci, 2, 28.
 Risk factors for
respiratory
depression

Sultan, P., Gutierrez, M. C., & Carvalho, B. (2011). Neuraxial morphine and respiratory
depression. Drugs, 71(14), 1807-1819.
Bioavailability of opioids in the intrathecal and
epidural compartments is determined primarily
by the drug’s hydrophobicity.

Morphine demonstrate greater spread as a result of

slower uptake and elimination from the CSF

Sultan, P., Gutierrez, M. C., & Carvalho, B. (2011). Neuraxial morphine and respiratory
depression. Drugs, 71(14), 1807-1819.
 Opioid spinal cord bioavailability after
neuraxial administration
Bujedo, B. M. (2013). Recommendations for spinal opioids clinical practice in the
management of postoperative pain. J Anesthesiol Clin Sci, 2, 28.
 1 High CSF bioavailability
Pharmacokinetics of
neuraxial morphine 2 Excellent spinal penetration

3 Prolonged duration

4 Less systemic absorption

than lipophilic opioids

Sultan, P., Gutierrez, M. C., & Carvalho, B. (2011). Neuraxial morphine and respiratory
depression. Drugs, 71(14), 1807-1819.
 Hip surgery
Neuraxial 0.1

Knee replacement
morphine has an 0.2

analgesic efficacy
Cholecystectomy
0.12

‘ceiling’
TAHBSO
0.3

Cesarean delivery
Dose-response studies reveal optimal 0.1

‘single-shot’ morphine dose: 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35

0.075-0.15 mg (intrathecal)
2.5-3.75 mg (epidural)

Sultan, P., Gutierrez, M. C., & Carvalho, B. (2011). Neuraxial morphine and respiratory
depression. Drugs, 71(14), 1807-1819.
Prevention of Respiratory Depression
after Neuraxial Opioid Administration

Identify patients at risk for

Consider drug selection
respiratory depression

Monitor for adequacy of Use multimodal adjuvant

ventilation, oxygenation, analgesia to reduce dose
level of consciousness requirements

Practice guidelines for the prevention, detection, and Management of Respiratory Depression
Associated with Neuraxial Opioid Administration: an updated report (2017)
 • Focused history
• Extremes of age
Identify patients • Obstructive sleep apnea: STOP-
at risk for BANG questionnaire
respiratory • Co-existing diseases or
depression conditions: obesity, abdominal
distension, COPD
• Current medications: sedatives,
preoperative opioid use
• Adverse effects after opioid
administration
 • Physical examination
• Baseline vital signs
Identify patients • Airway, heart, lung, and cognitive
at risk for function
respiratory
depression
 • Age is an important predictor of
postoperative opioid requirements
• ⬇TBW, ⬆ body fat

• Morphine-6-glucuronide depends
on renal excretion
• Enhanced analgesia in older
patients

Clinical pharmacology of opioids

in older patients

Miller's Anesthesia 8E (2015) p. 2418

 Drug selection
01 Route of administration
Single-injection neuraxial opioids
may be safely used in place of
parenteral opioids
- Fentanyl vs morphine
Continuous epidural opioids are
preferred to parenteral opioids
Practice guidelines for the prevention, detection, and Management of Respiratory Depression
02 Type of drug
Match the appropriate duration
of drug monitoring with its
pharmacokinetic effect
Do not administer neuraxial
morphine/ hydromorphine to
outpatient surgical patients
Associated with Neuraxial Opioid Administration: an updated report (2017)
 Drug selection
03 Dose selection 04 Drug combinations

Administer lowest efficacious Concomitant administration

dose to minimize risk of parenteral opioids,
sedatives, hypnotics or
magnesium requires
increased monitoring

Practice guidelines for the prevention, detection, and Management of Respiratory Depression
Associated with Neuraxial Opioid Administration: an updated report (2017)
Monitoring for
respiratory Adequacy of
depression ventilation
(RR, depth of
Oxygenation
Increased monitoring respiration)
(intensity, duration, additional
methods) warranted for patients
at increased risk

Level of
sedation
(arousal,
concentration)

Practice guidelines for the prevention, detection, and Management of Respiratory Depression
Associated with Neuraxial Opioid Administration: an updated report (2017)
 Monitoring for
respiratory depression
Single-injection Minimum of 2 h after Continuous monitoring
q1 until 2 h
Lipophilic Opioid administration for first 20 mins
q1 until 12 h
Continuous Infusion with Monitor the entire Continuous monitoring
q2 from 12-24 h
Lipophilic Opioid time infusion is in use for first 20 mins
q4 after 24 h
Single-injection Minimum of 24 h after q1 until 12 h q2 from 12-24 h
Hydrophilic Opioid administration
q2 from 12-24 h
Continuous Infusion with Monitor the entire q1 until 12 h
q4 after 24 h
Hydrophilic Opioid time infusion is in use

Practice guidelines for the prevention, detection, and Management of Respiratory Depression
Associated with Neuraxial Opioid Administration: an updated report (2017)
 Multimodal analgesia
Use several agents or techniques,
each acting at different sites of the pain pathway

Reduces the dependence on a single medication and mechanism

0.025 mg of IT morphine + systemic diclofenac

found as effective as 0.05-0.1 mg IT morphine
 Management of
respiratory depression

Supplemental Reversal Noninvasive

positive pressure
oxygen agents ventilation
01 Supplemental oxygen
• Results in fewer hypoxic events
• Disadvantage: masks hypoventilation and
early detection of obstructive event

Barash, P. G. (Ed.). (2018). Clinical anesthesia. p.1337.

 02 Reversal agents
Naloxone: competitive mu-opioid receptor antagonist
• Indicated for symptomatic respiratory depression
(obtundation + RR < 8 breaths/min)
• 2 min onset, 30-45 min duration
• Highly lipid soluble = rapid uptake, rapid elimination
• Repeated boluses of 40 mcg; start infusion
(3-4 ug/kg/hr) to prevent re-narcotization

Ayad, S., et al. (2019). Characterisation and monitoring of postoperative respiratory depression:
current approaches and future considerations. British journal of anaesthesia, 123(3), 378-391.
 02 Reversal agents
Novel non-opioid reversal drugs
• Serotonin receptor agonists
• Ampakines (AMPA receptor modulators)
• Minocycline

Ayad, S., et al. (2019). Characterisation and monitoring of postoperative respiratory depression:
current approaches and future considerations. British journal of anaesthesia, 123(3), 378-391.
03 Noninvasive positive
pressure ventilation
Patients likely to benefit: younger age, lower acuity of illness,
able to cooperate, intact dentition, moderate hypercarbia
(PaCO2 45-92 mmHG), clinical improvement in 2 hours

Intubate if (1) airway protection at risk,

(2) failing oxygenation/ ventilation,
(3) anticipated clinical course require intubation
 Sedation
Other
complications of
Pruritus
adding adjuncts
to neuraxial
Nausea and vomiting
anesthesia

Urinary retention

GI dysfunction
SEDATION
• Associated with large doses
of intrathecal clonidine
• Peaks within 1-2 hrs, lasts
up to 8 hrs
• Hypotension, bradycardia
may require atropine
Most common SE of Present in trigeminal Nalmefene 10-25 mcg,
intrathecal opioid distribution (eyes and nalbuphine 1-5 mg,
administration nose) propofol 10 mg
(30-100%)

PRURITUS
 Exposed chemoreceptive trigger zone,
NAUSEA hypotension, delayed gastric empyting

AND
Risk factors:
• Adding phenylephrine/ epinephrine
• Peak block height >T5
VOMITING • Baseline HR >60 bpm
• History of motion sickness

Gehling, M., & Tryba, M. (2009). Risks and side-effects of intrathecal morphine
combined with spinal anaesthesia: a meta-analysis. Anaesthesia, 64(6), 643-651.
 Most frequent risk of N&V: morphine
NAUSEA Dose-dependent: use <0.1 mg morphine

AND Observed in intrathecal neostigmine (bradycardia,

LE weakness at higher doses)

VOMITING Prophylaxis: ondansetron 8 mg, dexamethasone 8

mg, haloperidol 1 mg

Gehling, M., & Tryba, M. (2009). Risks and side-effects of intrathecal morphine
combined with spinal anaesthesia: a meta-analysis. Anaesthesia, 64(6), 643-651.
URINARY RETENTION
1 Occurs in 1/3 of patients

2 S2, S3, S4 blockade =

weakened detrusor muscle

3 Associated with age, male

gender, intrathecal morphine
GASTROINTESTINAL
DYSFUNCTION
• Opioid receptors present in enteric plexus of GI tract
• Inhibit intestinal, pancreatic secretion
• Increase bowel tone
• Decrease intestinal propulsive activity (constipation)
• Spasms of sphincter of Oddi, CBD (colic-like complaints)
CASE MANAGEMENT
ASSESSMENT
• 78-year-old patient • Targeted
Arousal from
history
sedation
and PE to
• identify
Supplemental
risk factors
oxygenfor
• Partial hip replacement surgery • respiratory
Maintain IVdepression
access
• Under spinal anesthesia with 0.5% • •Monitor
Extreme for adequacy
of age of
bupivacaine and 0.1 mg of •ventilation,
Weight, OSA oxygenation,
signs andlevel of
consciousness
symptoms
morphine • •Reversal
Coexisting
agentsdiseases
should be
• Later that evening, she appears •available
Current medications
extremely sleepy with O2 sat of • Noninvasive positive pressure
• Consider
ventilationroute of administration,
92% on nasal cannula type of drug, dose selection,
drug combinations
 Barash, P. G. (Ed.). (2018). Clinical anesthesia.

Bujedo, B. M. (2013). Recommendations for spinal opioids clinical practice in the

management of postoperative pain. J Anesthesiol Clin Sci, 2, 28.

References Charuwattanapanit, I. (2020). Neuraxial Morphine: A review of Mechanism of

Action and Respiratory Depression. Thai Journal of Anesthesiology, 46(4), 245-
260.

Gehling, M., & Tryba, M. (2009). Risks and side-effects of intrathecal morphine
combined with spinal anaesthesia: a meta-analysis. Anaesthesia, 64(6), 643-651.

Miller's Anesthesia 8E (2015)

Practice guidelines for the prevention, detection, and Management of

Respiratory Depression Associated with Neuraxial Opioid Administration: an
updated report (2017)

Side effects of Opioid Medications: Calgary Guide (2015)

https://calgaryguide.ucalgary.ca/Side-Effects-of-Opioid-Medications/

Sultan, P., Gutierrez, M. C., & Carvalho, B. (2011). Neuraxial morphine and
respiratory depression. Drugs, 71(14), 1807-1819.