Ketamine for intraoperative and postoperative analgesia

I’m always looking for ways to improve myself. Lately, I’m looking at various clinical elements of my practice and select certain endpoints that will better my practice of medicine.

This time, I’ve focused on cutting back on opioids intraoperatively for pain. I’m looking specifically at ketamine, an old drug with multiple benefits (and some downsides). Not only does ketamine help with intraoperative pain, but it also helps with postoperative pain. I’d like to incorporate some type of ERAS model for all of my patients and surgeries.

ketamine_hydrochloride_050

Ketamine: (different doses I’ve seen in the literature below)

• Induction: 0.2-0.5 mg/kg

• Infusion: 0.1mg/kg/hr before incision

◦ 2mcg/kg/hr x 24hr (spine)

◦ 0.1-0.15mg/kg/hr x 24-72hrs (UW)

◦ 2mcg/kg/min

◦ 2-8mcg/kg/min


What I’m using nowadays:

  • Oct 2017:
    • Cardiac open hearts: induction bolus=0.5mg/kg + infusion=0.1mg/kg/hr and stopping when last stitch placed. Patients seem to require less postoperative narcotics. Looking at time to extubation to see if this is improved.  Time to extubation seems the same as my prior non-ketamine patients because RT and RNs follow a weaning protocol.  Patients are more comfortable and require less pain medication.
  • Dec 2018:
    • Cardiac open hearts: induction bolus = 0.5 mg/kg + another 0.5 mg/kg bolus when re-warming; infusion 0.2 mg/kg/hr stopping when last dressing placed.
  • July 2019:
    • Cardiac open hearts: induction bolus = 1 mg/kg + 0.5mg/kg bolus pre-CPB.  No infusion.  This formula is roughly in between the bolus (0.5mg/kg) + infusion (0.1mg/kg/hr and 0.2mg/kg/hr) for <5hr case.  For hearts >5hr, add 0.25-0.5mg/kg bolus when re-warming (0.5mg/kg dosing roughly approximates a 7hr case).
  • Sept 2019:
    • Cardiac open hearts: No induction bolus.  1mg/kg bolus prior to incision.  0.5mg/kg bolus pre-CPB.  0.25-0.5mg/kg bolus rewarming on CPB based on length of case (see July 2019 notes).

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Is intravenous ketamine effective for postoperative pain management in adults? Medwave2017;17(Suppl2):e6952 doi: 10.5867/medwave.2017.6952

Ketamine: Current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014 Sep-Dec; 8(3): 283–290.

Effect of intraoperative infusion of low-dose ketamine on management of postoperative analgesia. J Nat Sci Biol Med. 2015 Jul-Dec; 6(2): 378–382.

Ketamine for Perioperative Pain Management. Anesthesiology 2005; 102:211–20.

CLINICAL GUIDELINE FOR USE OF KETAMINE AS AN ADJUVANT ANALGESIC FOR USE BY ANAESTHETISTS ONLY. NHS Royal Cornwall Guidelines June 2015.

Ketamine as an Adjunct to Postoperative Pain Management in Opioid Tolerant Patients After Spinal Fusions: A Prospective Randomized Trial. HSS Journal: Volume 4, Number 1.

The Use of Intravenous Infusion or Single Dose of Low-Dose Ketamine for Postoperative Analgesia: A Review of the Current Literature. Pain Medicine Volume 16, Issue 2, pages 383–403, February 2015.

Role of Ketamine in Acute Postoperative Pain Management: A Narrative Review. BioMed Research International. Volume 2015; Article ID 749837, 10 pages.

 

Ketamine in Pain Management. CNS Neuroscience & Therapeutics 19 (2013) 396–402.

Ketamine for the Management of Acute Pain and Agitation in the ICU: Future, Fiction or Just another Drug-Induced Hallucination? Ann Pharmacol Pharm. 2017; 2(11): 1059.

Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet 2017; 390: 267–75.

A comparison between intravenous lidocaine and ketamine on acute and chronic pain after open nephrectomy: A prospective, double-blind, randomized, placebo-controlled study. Saudi J Anaesth 2017;11:177-84.

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Acute and Chronic Post-Thoracotomy Pain, modes of treatment

Another project I’m working on is the effect of lidocaine infusions on intraoperative and postoperative pain.


***UPDATE July 8, 2018 ***

AnesthesiologyNews: July 2018: New Consensus Guidelines Issued for Use of IV Ketamine for Acute Pain.

  • Question 1: Which patients and acute pain conditions should be considered for ketamine treatment?
    Conclusion: For patients undergoing painful surgery, subanesthetic ketamine infusions should be considered. Ketamine also may be warranted for opioid-dependent or opioid-tolerant patients undergoing surgery, or with acute or chronic sickle cell pain. For patients with sleep apnea, ketamine may be appropriate as an adjunct to limit opioid use.
  • Question 2: What dose range is considered subanesthetic, and does the evidence support dosing in this range for acute pain?
    Conclusion: Ketamine bolus doses should not exceed 0.35 mg/kg, whereas infusions for acute pain generally should not exceed 1 mg/kg per hour in settings lacking intensive monitoring. However, dosing outside this range may be indicated because of an individual patient’s pharmacokinetic and pharmacodynamic factors and other considerations, such as prior ketamine exposure. However, ketamine’s adverse effects prevent some patients from tolerating higher doses for acute pain; therefore, unlike for chronic pain management, lower doses in the range of 0.1 to 0.5 mg/kg per hour may be necessary to achieve an acceptable balance between analgesia and adverse events.
  • Question 3: What is the evidence to support ketamine infusions as an adjunct to opioids and other analgesic therapies for perioperative analgesia?
    Conclusion: There is moderate evidence to support using subanesthetic IV ketamine bolus doses up to 0.35 mg/kg and infusions up to 1 mg/kg per hour as adjuncts to opioids for perioperative analgesia.
  • Question 4: What are the contraindications to ketamine infusions in the setting of acute pain management, and do they differ from chronic pain settings?
    Conclusion: Patients with poorly controlled cardiovascular disease or who are pregnant or have active psychosis should avoid ketamine. Similarly, for hepatic dysfunction, patients with severe disease, such as cirrhosis, should not take the medicine; however, ketamine can be given with caution for moderate disease by monitoring liver function tests before infusion and during infusions in surveillance of elevations. On the other hand, ketamine should not be given to patients with elevated intracranial pressure or elevated intraocular pressure.
  • Question 5: What is the evidence to support nonparenteral ketamine for acute pain management?
    Conclusion: Intranasal ketamine is beneficial for acute pain management by achieving effective analgesia and amnesia/procedural sedation. Patients for whom IV access is difficult and in children undergoing procedures are likely candidates. But for oral ketamine, the evidence is less convincing, although anecdotal reports suggest this route may provide short-term advantages in some patients with acute pain.
  • Question 6: Does any evidence support IV ketamine patient-controlled analgesia (PCA) for acute pain?
    Conclusion: The evidence is limited to support IV ketamine PCA as the sole analgesic for acute or periprocedural pain. There is moderate evidence, however, to support the addition of ketamine to an opioid-based IV PCA regimen for acute and perioperative pain therapy.

New guidelines for the use of IV ketamine infusions for acute pain management have been published as a special article in Regional Anesthesia and Pain Medicine (2018;43[5]:456-466).

The guidelines were jointly developed by the American Society of Regional Anesthesia and Pain Medicine (ASRA), the American Academy of Pain Medicine and the American Society of Anesthesiologists.


Update Nov, 30, 2018

Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Regional Anesthesia and Pain Medicine: July 2018 – Volume 43 – Issue 5 – p 456–466

Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists.  Regional Anesthesia and Pain Medicine: July 2018 – Volume 43 – Issue 5 – p 521–546


Updated Sept 2019

Postoperative pain management in patients with chronic kidney disease. . 2015 Jan-Mar; 31(1): 6–13

Ketamine and CKD

Ketamine is an N-methyl-d-aspartate receptor antagonist that is commonly used as an adjunct for the treatment of acute postoperative or posttraumatic pain to improve pain scores and reduce opioid consumption by approximately 30-50%.[] Certain patients seem to benefit more from the addition of ketamine, including those with chronic neuropathic pain, opioid dependence or tolerance and acute hyperalgesia.[] 8% of administered ketamine is metabolized by the liver forming norketamine, which possess only 20-30% of the potency of ketamine. Norketamine is then hydroxylated into a water-soluble metabolite excreted by the kidney.[] Most clinicians believe that dose modification for ketamine is not required for patients with decreased renal function.[,

 

 

Methadone and Acute and Chronic Pain Management

We had a journal club where we discussed this article: Anesthesiology, May 2017; Clinical effectiveness and safety of intraoperative methadone in patients undergoing posterior spinal fusion surgery: a randomized, double-blinded, controlled trial.

  • IV Methadone 0.2 mg/kg vs IV hydromorphone 2mg at surgical closure in 2+ level spinal fusion
  • Decreased postop IV and opioid requirements and pain scores.  Improved patient satisfaction

Questions:

  1. Is there a pain service following these patients postoperatively?
  2. Exclusions: do you include OSA and BMI>45 patients?
  3. Is ETCO2 and PCA enough to combat respiratory depression on the floor?
  4. Are any discharged on the same day after receiving this dose — think total knees and single level lamis?
  5. Will this improve or worsen the opioid epidemic?
  6. Are surgeons on board with tackling pain multimodally for the benefit of the patient?
  7. For pain follow-up, are there psychiatry, homeopathy, palliative care, PT, holistic approaches for the patient?

Methadone Dose Conversion Guidelines

Intraop Lidocaine for postop pain

Intraop Ketamine for postop pain

Literature search:

Sys Rev 2014: Effectiveness of opioid substitution treatments for patients with opioid dependence: a systematic review and multiple treatment protocol.

Am j of Pub Health, Aug 2014. Determinants of Increased Opioid-Related Mortality in the United States and Canada, 1990–2013: A Systematic Review.

Br J Clin Pharmacol. 2014 Feb; 77(2): 272–284. Long term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack?

PLoS One. 2014; 9(11): e112328. Methadone Induction in Primary Care for Opioid Dependence: A Pragmatic Randomized Trial (ANRS Methaville).

Curr Psychiatry Rev. 2014 May; 10(2): 156–167. Genetics of Opioid Dependence: A Review of the Genetic Contribution to Opioid Dependence. 

Drug Alcohol Depend. 2016 Mar 1; 160: 112–118. Methadone, Buprenorphine and Preferences for Opioid Agonist Treatment: A Qualitative Analysis. 

Croat Med J. 2013 Feb; 54(1): 42–48. Risk factors for fatal outcome in patients with opioid dependence treated with methadone in a family medicine setting in Croatia. 

J Med Toxicol. 2016 Mar; 12(1): 58–63. Pharmacotherapy of Opioid Addiction: “Putting a Real Face on a False Demon”. 

Syst Rev. 2014; 3: 45. Sex differences in outcomes of methadone maintenance treatment for opioid addiction: a systematic review protocol.

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