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Opioid-free Perioperative
Pain Management
D. John Doyle MD PhD
Chief, Department of General Anesthesia
Cleveland Clinic Abu Dhabi
Professor of Anesthesiology
Cleveland Clinic
Much of what is known about opioid-free
perioperative pain management comes to us
from the Enhanced Recovery literature.
17 Elements to ERAS
8 ERAS Elements Pertain Specifically to Anesthesia
Nonopiate Pain Management
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Local and regional anesthesia
Systemic lidocaine
Acetaminophen
NSAIDS (e.g., ketorolac)
Corticosteroids
Ketamine
Magnesium
α2 Adrenoceptor Agonists (clonidine and dexmedetomidine )
Gabapentinoids (gabapentin and pregabalin)
Corticosteroids
http://www.medscape.com/viewarticle/811736_7
able 2. Summary of clinical benefits
Drug
Summary of clinical benefits
Ketamine
•Useful adjuvant in painful procedures: upper abdominal, thoracic, and major orthopaedic surgeries (Level I)5
•Useful adjuvant to PCA analgesia (Level I)1
•Patients with chronic pain issues and on high-dose opioids—decreases pain intensity and opioid consumption lasting
much beyond the perioperative period (Level II) 17
•Opioid-resistant pain—rescue analgesia (mixed evidence; Level II) 1
•Has preventive but not pre-emptive analgesic effect (Level I). Studies looking at the role of ketamine in preventing
CPSP have shown only mixed effects (Level II)1
Pregabalin
•Risk–benefits probably more acceptable for painful procedures resulting in acute neuropathic pain, requiring large
doses of opioids (e.g. cardiothoracic surgery, arthroplasty, or spine surgery) in order for the reduction in opioid-related
side-effects to outweigh the side-effects. The evidence for this is limited and needs further research. Risks for minor,
laparoscopic, or day-care procedures probably outweigh the benefits 7
•Useful preventive analgesic effect9
Gabapentin
•Benefits similar to pregabalin, but being an older drug has more literature evidence
•Improved analgesia at rest and movement (Level I)
•Improved functional recovery with better range of movements and pulmonary function (Level II) 10
•Analgesic effect comparable and synergetic with NSAIDS and superior to tramadol 10
•Useful adjuvant to epidural analgesia—decreased pain scores, epidural analgesic consumption, and patient
satisfaction despite an increase in dizziness 1
•In established acute postoperative pain, single-dose gabapentin is superior to placebo but worse than other
commonly used analgesic. The NNT was 11 (Cochrane review) 18
•Useful preventive analgesic effect9
•A small RCT (60 patients undergoing abdominal hysterectomy) showed gabapentin was superior to ketamine in
preventing CPSP9
I.V. lidocaine
•Useful in visceral pain and improves postoperative bowel function after abdominal surgery—reduces pain and opioid
requirements, nausea, vomiting, duration of ileus, resulting in decreased time to pass flatus, faeces and earlier intake
of enteral food, rehabilitation, and discharge (Level I) 12,13
•Benefit seen even in patients undergoing laparoscopic colectomy as part of acute rehabilitation programme 12,13
•No proven use in non-abdominal surgeries12
•Probably has a preventive effect after major abdominal and breast surgery (Level II) 14,15
Systemic α2
agonist
•Moderate analgesic benefit—probably better than paracetamol but less than that of ketamine and NSAIDS as inferred
from non-systematic indirect comparison16
•All these beneficial effects may come at a price of significant hypotension and bradycardia 19
•Useful adjuvant in perioperative care in adults and children because of several useful extra analgesic benefits such as
sedation, anxiolysis, analgesia, postoperative shivering, PONV, agitation, mitigation of stress response to surgery and
tracheal intubation, anaesthetic-sparing effect, and as supplement to neuraxial and peripheral nerve blocks 16
•Decreased perioperative mortality and myocardial infarction especially in high-risk vascular surgeries19
•No evidence for preventive analgesia16
http://www.medscape.com/viewarticle/811736_5
Paracetamol
Lidocaine
Recent literature suggests
that an adjunctive
intraoperative lidocaine
infusion (100 mg
intravenously prior to
incision and then 1‐2
mg/kg/hour ) aids in
patient recovery after
surgery, presumably as a
result of its newly
discovered antiinflammatory properties.
POI = postoperative ileus
http://slideplayer.com/slide/6079619/
Intravenous Lidocaine
Contraindications
• First and second degree heart conduction blocks could be
aggravated or progress into a higher degree of heart block with
lidocaine administration.
• Cardiovascular instability and concomitant use of alpha agonists
(e.g., clonidine) or beta blockers (e.g., metoprolol, labetolol) are
relative contraindications.
• Allergies to other amide local anesthetics (bupivacaine).
• Allergy to Novacaine (procaine) is not a contraindication as
Novacaine is an ester local anesthetic.
• (Safety Warning: bupivacaine and ropivacaine are never given
intravenously).
http://prc.coh.org/FF%20LidoIVPer12-10.pdf
Intravenous Lidocaine
Contraindications
Unstable coronary disease
Recent MI
Heart failure
Heart block
Electrolyte disturbances
Liver disease
Cardiac arrhythmia disorders
Seizure disorders
https://www.mc.vanderbilt.edu/documents/periopservices/files/
Lidocaine%20Infusion%20PP%20for%20HR-PACU.pdf
May One Give a Lidocaine Infusion
on a General Care Floor?
Must be approved by the
Pharmacy and Therapeutics
Committee (similar issue for
ketamine).
IV lipid emulsion (20%)
therapy should be available
(lipidrescue.org).
Intravenous Lidocaine References
• Groudine, S.B., Fisher, H.A.G., Kaufman, R.P., Patel, M.K., Wilkins, L.J., Mehta, S.A., Lumb,
P.D. (1998). Intravenous lidocaine speeds the return of bowel function, decreases
postoperative pain, and shortens hospital stay in patients undergoing radical retropubic
prostatectomy. Anesthesia and Analgesia; 86:235‐239.
• Herroeder, S., Pecher, S., Schonherr, M.E., Kaulitz, G., Hanenkamp, K., Friess, H., Bottiger,
B.W., Bauer, H., Dijkgraaf, M.G.W., Durieux, M.E., Hollman, M.W. (2007). Systemic lidocaine
shortens length of hospital stay after colorectal surgery. Annals of Surgery, 246(2), 192‐200.
• Kaba, A., Laurent, S.R., Detroz, B.J., Sessler, D.I., Durieux, M.E., Lamy, M.L., Joris, J.L.
(2007). Intravenous lidocaine infusion facilitates acute rehabilitation after laparoscopic
colectomy. Anesthesiology, 106:11‐18.
• Koppert, W., Weigand, M., Neumann, F., Sittl, R., Schuettler, J., Schmelz, M., Hering. (2008).
Perioperative intravenous lidocaine had preventive effects on postoperative pain and morphine
consumption after major abdominal surgery. Anesthesia and Analgesia, 98:1050‐1055.
• Martin, F., Cherif, K., Gentilli, M.E., Enel, D., Abe, E., Alvarez, J.C., Mazoit, J.X., Chuvin, M.,
Bouhassira, D., Fletcher, D. (2008). Lack of impact of intravenous lidocaine on analgesia,
functional recovery, and nociceptive pain threshold after total hip arthroplasty. Anesthesiology,
109:118‐123.
• Yardeni IX, Beilin B, Mayburd E, Levinson Y, Bessler H. the effect of perioperative intravenous
lidocaine on postoperative pain and immune function. Anesthesia &Analgesia
2009;109(5):1464‐1469.
Ketamine
Ketamine is an NMDA receptor antagonist, but it also acts at other sites
(including opioid receptors and monoamine transporters).
Ketamine comes as a racemic mixture consisting two enantiomers, Rand S-ketamine. Pure S-ketamine (availabale in Europe) is reported to be
less prone to psychomimetic side effects, such as derealisation and
hallucinations.
Posterior spine fusion study
Give 0.2 mg/kg on induction of general anesthesia
and then 2 mcg/kg/hour for the next 24 hours.
“Perioperative infusion of subanesthetic ketamine
was effective in reducing pain in narcotic-tolerant
patients after posterior spinal fusions. It reversed
unacceptable levels of pain in patients resistant to
conventional narcotic treatment.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504281/
http://www.ebmedicine.net/topics.php?paction
=showTopicSeg&topic_id=247&seg_id=4803
Journal of Anaesthesiology Clinical Pharmacology
| April-June 2016 | Vol 32 | Issue 2
Therapy For Depression And Chronic Pain
3-Day Ketamine Treatment for
Complex Regional Pain Syndrome
https://www.youtube.com/watch?v=IGqo5NBr_xw
https://www.youtube.com/watch?v=piiBg1K-bm0
Rapid Relief from Treatment
Resistant Depression with Oral
Ketamine
https://www.youtube.com/watch?v=7A26miRlYBc
Gabapentin and Pregabalin
“Gabapentinoids mainly act on the α-2-δ-1
subunit of pre-synpatic calcium channels
and inhibit neuronal calcium influx. This
results in a reduction in the release of
excitatory neurotransmitters such as
glutamate, substance P, and calcitonin generelated peptide from primary afferent nerve
fibres thus suppressing neuronal excitability
after nerve or tissue injury. ”
http://www.medscape.com/viewarticle/811736_3
Magnesium
Systemic administration of
perioperative magnesium reduces
postoperative pain and opioid
consumption.
De Oliveira GS Jr, Castro-Alves LJ, Khan JH, McCarthy
RJ. Perioperative systemic magnesium to minimize
postoperative pain: a meta-analysis of randomized
controlled trials. Anesthesiology. 2013 Jul;119(1):17890.
Dexamethasone
Single dose IV dexamethasone at
doses over 0.1 mg/kg is an effective
adjunct to reduce postoperative pain
and opioid consumption after surgery.
De Oliveira GS Jr, Almeida MD, Benzon HT, McCarthy RJ.
Perioperative single dose systemic dexamethasone for
postoperative pain: a meta-analysis of randomized controlled
trials. Anesthesiology. 2011 Sep;115(3):575-88.
“In summary, we found that perioperative singledose dexamethasone was associated with small but
statistically significant reductions in postoperative
pain, postoperative opioid consumption, need for
rescue analgesia, PACU stays, and a longer time to
first analgesic dose. The effect on postoperative
opioid consumption was not dose-dependent. In
addition, we found no increased risk of infection or
delayed wound healing, although dexamethasone
was associated with slight hyperglycaemia on the
first postoperative day.”
Dexmedetomidine
Sixty-four patients scheduled for abdominal hysterectomy under general
anesthesia were divided into two groups that were maintained using
propofol/remifentanil/dexmedetomidine (PRD) or propofol/remifentanil/ saline
(PRS). During surgery, patients in the PRD group had a lower bispectral index
(BIS) value, which indicated a deeper anesthetic state, and a higher sedation
score immediately after extubation than patients in the PRS group