Intra- and Post-Operative Ketamine Use

Andrew W. Gorlin, Assistant Professor of Anesthesiology, Mayo Clinic College of Medicine

Ketamine is an NMDA antagonist which, when administered intravenously at sub-anesthetic doses (≤0.3mg/kg bolus or ≤0.3mg/kg/hr infusion), provides analgesia and has a significant opioid sparing effect in the perioperative setting.  There is also evidence that ketamine is useful in treating acute pain in patients who are opioid tolerant.  Sub-anesthetic infusions of ketamine can be safely administered on standard medical-surgical units.

Perioperative indications for ketamine infusion:

• Very painful procedures
• Intractable opioid-resistant pain
• Highly opioid tolerant patients
• Clinical need to minimize opioids
• High risk for persistent post-surgical pain (eg amputation, thoracotomy, etc)

Ketamine Pros:

• Non-opioid analgesic which reduces perioperative opioid consumption
• At sub-anesthetic doses has minimal hemodynamic effects
• At sub-anesthetic doses has no effect on respiratory drive or airway patency

Ketamine Cons:

• Low-moderate incidence (7-16%) of psychomimetic effects such as hallucinations and dysphoria
• Low incidence of diplopia (4-9%)
• Especially when administered in combination with other CNS depressants may contribute to sedation

Ketamine contraindications

• History of psychosis
• Unstable cardiovascular disease
• Liver or renal failure

How to administer ketamine:

Intraoperatively: Anesthesia team can give single bolus with induction and/or serial boluses (every 30-60 minutes) in the operating room (initial 0.3mg/kg and then subsequent 0.1-0.3mg/kg boluses every 30-60 minutes)

• Post-operative infusion requires coordination with the OR, PACU, med-surg unit
  • Ketamine is a controlled substance and should be prepared in a secure storage system (such as a PCA cartridge) by pharmacy and administered by an infusion pump
  • Dose should be ≤0.3mg/kg/hr based on Ideal Body Weight; a good starting point for most patients is 10mg/hr
  • A separate IV is preferable though it can be safely “piggy-backed” onto another line as long as it is on a distal port (ie, close to the patient)
  • Side effects can be managed on a case by case basis but typically hallucinations and other complains will stop within an hour of stopping the infusion
  • Use of benzodiazepines to reduce psychomimetic effects is controversial and may cause more problems with sedation and delirium
  • AZ Board of Nursing required EKG monitoring for the duration of infusion, based on an “increase in scope” of nursing practice.

Lidocaine and Magnesium Infusions

Kim Nguyen, MD and McLean Beson, MD

Lidocaine

Summary: Amide local anesthetic.

• Hepatically cleared via CYP enzymes.
• Analgesic, antihyperalgesic and anti-inflammatory properties.
• Proposed mechanisms of action include blockade of sodium channels (analgesia), blockade of NMDA receptors (decreases acute hyperalgesia), glycinergic action (co-agonist at NMDA receptors), reduction in Substance P and proinflammatory cytokines (IL-6, IL-8) (anti-inflammatory)
• Peripherally decreases the amount of inflammatory mediators released during inflammatory processes.
• Central decreases in neuronal response to ascending pain pathways including those of dorsal root ganglion and primary afferent (C-fibers) nerve fibers/receptors.

Lidocaine Pros:

• Lower pain scores up to 24 hours post-op, lower incidence of nausea/vomiting, possible decrease in length of stay.
• Lower incidence of ileus: direct action on peritoneal nerves, reducing post-surgical peritoneal irritation, suppressing inhibitory GI reflexes leading to ileus.

Lidocaine Cons:

• Hepatically cleared, which means decreases in hepatic function (cirrhosis) or decreased liver blood flow (CHF, B-blockade, H2 receptor blockage) can potentially reduce rates of metabolism leading to higher blood concentration and greater risk of systemic toxicity
• LAST (Local Anesthetic Systemic Toxicity): classically described as prodromal circumoral numbness, dizziness, tinnitus, visual disturbances worsening to altered mental status, CNS depression and respiratory and/or cardiac arrest.

Contraindications:

• Avoid in patients with: heart block (further cardiac Na channel inhibition could lead to worsening degree of block), unstable CAD, recent MI, CHF, electrolyte abnormalities, cardiac arrhythmia disorders or seizure disorders.
• Avoid in patients with decreased liver function.
• Avoid infusion if planned co-administration of other long lasting local anesthetics (liposomal Bupivacaine, etc) as mixtures of local anesthetics are considered to have additive toxic effects.

How to administer intra-op:

• Initial bolus: 100mg or 1-2mg/kg
• Continuous infusion: 1-2mg/kg/hr or 2-3 mg/min
• Can be continued into the post-operative period but should remain on cardiac monitor due to potential systemic/cardiac toxicity.

Magnesium

Magnesium is an NMDA antagonist that regulates Ca influx into cells and can be used to suppress neuropathic pain in the perioperative period. When given with morphine or ketamine, it has a synergistic effect and helps decrease tolerance to morphine. Studies like the one from University of Toronto found that patients that had intraoperative magnesium infusion had decreased morphine intake by 24% and decreased pain scores overall up to at least 24 hours post op (Albrecht et al 2013). Another interesting study worth mentioning is from Seoul University, which included 900 TKA patients and found that those who received magnesium infusions intra-op had lower rates (by 62%) of chronic post-surgical pain syndrome at one year than those that did not receive it (Oh et al 2019).

Perioperative indications for magnesium infusion:

• Opioid-limiting strategy in cases where that would be ideal (Ex. bowel resection)
• Opioid-tolerant patients
• Decrease risk of post-operative chronic pain

Magnesium Pros:

• Can potentiate non-depolarizing neuromuscular blocking agents by competing for calcium channels in pre-synaptic nerve terminal
• Increases arteriolar vasodilation with minimal venous dilation which maintains cardiac output (1)
• Can help to decrease catecholamine-induced arrhythmias (1)
• Can aid in decreasing anesthetic requirements (1)
• Decreased incidence of post-op nausea/vomiting (1) which could also be due to less opioid and/or anesthetic gas use

Magnesium Cons:

• Does not provide great analgesia when administered alone
• When administered in supratherapeutic amounts, can develop lethargy, muscle weakness, respiratory depression. Occurs mainly in patients with renal failure
• Can cause transient hypotension especially when large boluses are given at one time

Magnesium Contraindications:

• Myasthenia Gravis
• AV conduction defect
• Relative: renal failure which can cause hypermagnesemia

How to administer magnesium:

• To be used in conjunction with other agents for pain control:
• Bolus: 30-50mg/kg over 15 minutes
• Infusion: 6-20mg/kg/hr until end of surgery

Other citations besides video:

1. Magnesium: an emerging drug in anaesthesia. James, M.F.M. British Journal of Anaesthesia, Volume 103, Issue 4, 465 - 467