The significance of pain control in enhanced recovery after surgery (ERAS) was first described by George Washington Crile in 1912. He observed that outcomes for patients who received ether anesthesia alone for surgery did very poorly compared to those who also received nitrous oxide and/or morphine. The best outcomes, he noted, were in patients who received cocaine nerve blocks and ether anesthesia. It was not until 1923 when Cuthbertson described the neuroendocrine stress response that the reasons for Dr. Crile’s observations became clear.
The modern day ERAS concept was popularized by Henrik Kehlet, a Danish surgeon, in the 1970’s. It caught on in Scandinavia, then Europe, other developed nations and eventually reached the USA. There are many different ways to enhance surgical recovery. Their common focus is on reducing physiologic stress using pre, intra and post-operative interventions. Surgical and post-procedural pain are obvious physiologic stressors.
The ERAS concept has led to ERAS protocols. These should be customized to the physiologic stressors inherent in the surgery/procedure and to the needs of the individual patient…read…ONE SIZE DOES NOT FIT ALL. Thus, it is important to understand the role of each element of a given ERAS protocol and utilize it appropriately.
The first ERAS protocol introduced at UVA was for colo-rectal surgery in adults. For the purposes of this article, I will focus on the pain control portion of this pathway. As I mentioned before, there are many ways to achieve enhanced recovery not all of which are incorporated in this particular protocol, e.g. epidural analgesia. Multi-modal approaches are preferred as these reduce side effects while maintaining efficacy.
Preoperatively, patients with complex pain problems and those on buprenorphine for addiction management are assessed in the Pre-operative Evaluation and Testing Clinic (PETC). Advice is given regarding medication use leading up to surgery and the Acute Pain Service (APS) is made aware of the patient’s planned date of admission. This facilitates an APS evaluation of these patients in the PACU and on the floor post-operatively.
On the day of surgery, prior to induction of general anesthesia, patients receive oral acetaminophen 975 mg, celecoxib 200 mg, and gabapentin 600 mg followed by intrathecal morphine (250 micrograms).
Intraoperatively, patients receive a bolus dose of ketamine (0.5 mg/kg) followed by an infusion at 0.1 – 0.3 mg/kg/h; a bolus dose of lidocaine 1 mg/kg followed by an infusion of 2 – 3 mg/min; and, 2 g IV magnesium. Dexamethasone 4 mg IV for anti-emesis but which also has an anti-inflammatory effect. Local anesthetic is infiltrated into the wound(s) during closure.
Postoperatively, the lidocaine infusion is continued at 0.5 – 1 mg/min for approximately 48 hours. Acetaminophen 1 g IV or 975 mg po q 6 h, and celecoxib 200 mg po q day or ketorolac 30 mg q 8 h, are continued as scheduled medications. Ketamine, midazolam and oxycodone are prescribed per protocol for the PACU. Oxycodone is prescribed for break through pain as needed on the floor.
What is the rationale for using these drugs?
Figure 1 provides a simplified overview of the pharmacological effects of these drugs. Under normal conditions, there is no sensation without a stimulus. As a tactile stimulus increases the sensation created also increases until the point where it becomes uncomfortable, painful and agonizing (line A). In situations with baseline inflammation the stimulus/sensation line is moved to up and to the left (line B). Thus, there is pain without a stimulus and tactile stimuli are associated with allodynia and hyperalgesia. Treating an inflammatory pain with an anti-inflammatory drug will move line B down to line A. An anti-inflammatory drug will not reduce sensation to below normal. Thus, if after using an anti-inflammatory drug(s) the sensation is still painful or too uncomfortable, an analgesic (line C) is required.
Figure 1: Pharmacologic effects of drugs on sensation with stimulus
There are two classes of analgesic: opioids and local anesthetics. Analgesics can reduce inflammatory and non-inflammatory pain but, especially with opioids, the side effects are directly proportional to the dose given. Thus, by using anti-inflammatory drugs to treat inflammation, and using opioids to treat the remainder of the pain, the side effect burden is minimized.
Neuropathic pain represents a resetting of the central nervous system such that tactile sensations are more easily interpreted as allodynia and/or hyperalgesia (line D). It is sometimes termed “Wind-up” or central sensitization. This is the condition that exists when acute pain evolves into chronic pain. Depending on the type of surgery and pain definitions used acute post-surgical pain evolves into chronic pain in 30 – 70% of patients.
Typically, this sort of pain is treated with gabapentinoids, tricyclic antidepressants (TCA) and serotonin-norepinephrine reuptake inhibitors (SNRI). Selective serotonin reuptake inhibitors (SSRI) are not useful in treating pain per se, but may improve the pain experience through treatment of depression. During tissue trauma, e.g. surgery, the nervous system starts to become sensitized after 20 minutes of exposure to pro-inflammatory mediators, etc.
Placing the drugs into the Figure, acetaminophen, celecoxib, lidocaine infusion and dexamethasone all provide anti-inflammatory effects and bring line B back to line A. Non-steroidal anti-inflammatories would do the same. Intrathecal morphine and local anesthetic wound infiltration provide analgesia (line A to line C; line B to line C). Ketamine and magnesium block N-methyl D-aspartate (NMDA) receptors and guard against central sensitization (stops line A to line D). Gabapentin treats neuropathic pain and helps ease visceral discomfort (line D to line A).
Additionally, ketamine by its dissociative effects focuses the pain experience on nociception alone. By removing the patient’s appreciation of the emotional, psychological, spiritual and social elements of pain, the pain experience can be made much more manageable.
Experience with this protocol has led to some changes. Ketamine is sometimes withheld in the elderly and those with dementia to avoid altering their cognitive state, or only the bolus dose is given. Dexmedetomidine is substituted in some cases. Gabapentin has an NNT of 6 and causes prolonged sleepiness in drug naïve patients at the 600 mg dose.
Although many studies have shown benefit in the immediate post-operative period, more recent work shows this is not sustained in terms of long term pain control and improved function. Thus, several protocols at UVA are being revised to omit single dose gabapentin. The consequences of this change in patient outcomes is awaited.
Understanding the concepts of enhanced recovery and the role of each component in a protocol allows the best customized care for each patient. Drug treatment of pain should address all the types of pain expected. The drug mixture is not as important as the pharmacological targets. Local anesthetic infiltration and blocks are best but limited in many instances.
ERAS protocols are not check lists. Customization is required.