Conference Lectures

               POST OPERATIVE PAIN MANAGEMENT –An Overview

DR SUSHIL.KRISHNAN MBBS;MD(Anesth)      Senior DMO(SG)/Anesth/                         Northern Railway Central Hospital-N DELHI

Acute and postoperative pain has been a focus of interest for anesthesiologists for many decades. Postoperative pain produces acute adverse physiologic effects with manifestations on multiple organ systems that can lead to significant morbidity both in the short term as well as the long term
Complications of inadequate  pain management has serious consequences and can include the following immediate sequlae- splinting; hypoxia; atelectasis; increased risk for pneumonia; hypertension and tachycardia (risk factors for cardiac ischemia and postoperative stroke); nausea and vomiting; ileus; muscle wasting; urinary retention;  Intermediate to long term sequlae would include immunologic depression; possible tumor recurrence; anxiety and/or depression; posttraumatic stress disorder; progression to  chronic pain.
A  much cited study (Apfelbaum2003)showed that 40% of patients had moderate to severe pain in immediate postoperative period; and 25% noted significant side effects from pain medications .More  than 80% patients surveyed noted pain in first 2 wk after surgery; 87% of those stated the pain  to be moderate to severe. A decade later postoperative pain is  still very common after surgery, varying from mild to very severe;
Briefly  the  etiology of post operative pain includes damage to nociceptive receptors at surgical site; release of inflammatory mediators; traction on internal organs; visceral pain and dynamic postsurgical pain.The  transmission pathways include rapid Aδ fibers and C fibers and  multiple neurotransmitters are involved  in pain transmission.
Assessment--A pain assessment tool should always  be used. which should:be easily understood by patients and staff;  quick to apply and offer a sensitive, reliable and valid measure. Visual analogue (VAS) and numerical rating scales (NRS) are used in practice although they have many shortcomings.
Pharmacological management of Acute Postoperative Pain
Acute postoperative pain management should start with a nonopioid analgesic drug for mild pain; Nonopioid analgesics in common use are the following: paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs and COX-2 inhibitors (coxibs)),     
Paracetamol is the first line drug and it is  the nonopioid drug with the least adverse effects when used in appropriate doses orally,rectally, or by i.v. infusion. Paracetamol reduces the consumption of opioids. It blocks production of neurotransmitting prostaglandins in spinal cord  It is commonly recommended that paracetamol should be used with caution or in reduced doses in patients with active liver disease,. However, others report that it can be used safely in patients with liver disease and is preferred to NSAIDs in such patients.
We can add a drug from another class of nonopioid analgesics for mild-to-moderate pain eg (NSAIDs). NSAIDs inhibit production of inflammatory-mediating prostaglandins peripherally NSAIDs are contraindicated when patients have:        Actual or potential bleeding problems; History of gastrointestinal ulceration; Aspirin-sensitive asthma; Significant renal impairment; Hypovolemia; Hyperkalemia;  Severe liver dysfunction.                                                                              They have to be used with caution in:           Elderly patients (above 65–70 years), who often have significant renal impairment; Diabetic patients (renal impairment likely); Patients with widespread vascular disease; Patients on ACE inhibitors etc                 In theory, drugs that have a more favorable COX-2:COX-1 activity ratio(Coxibs) should have a potent anti-inflammatory activity with fewer side effects. Although this is true ,the withdrawal of  some selective  COX-2 inhibitors from the market due to unwanted cardiovascular side effects shows that our  understanding of   the mechanism of action of  the NSAIDs  is still incomplete.
Opioids have long been the corner stone  of post operative pain relief but are now falling into disfavor .Their advantages include low cost; excellent effectiveness for acute pain and  the linear dose response with no ceiling for analgesic effect( for pure agonists). However their side effects and tolerance limit use .These include nausea and vomiting, respiratory depression, somnolence, constipation,ileus , urinary retention and delirium(in elderly patients)  Also Opioids have pronociceptive  effects as well including the opioid-induced hyperalgesia which is well known and is  linked to surgical injury. “Weak” opioid analgesic drugs, such as codeine and tramadol, are often initially added to the nonopioid analgesics.For more severe pain, a potent opioid like morphine is added. Fentanyl  has  a lack of active metabolites and  a fast onset of action make it an attractive choice     
Common Pharmacologic  Adjuncts in Postoperative Pain  Management
Gabapentinoids (e.g.,gabapentin, pregabalin)   bind to the alpha-2 delta subunit of voltage-sensitive calcium channels in spinal cord and  decrease fast firing of secondary neurons thus reduce neuronal activity.They are effective for treatment of acute surgical pain .Gabapentin’soptimal doses is  not clear ; 300 to 1200 mg/day is used ;  it is often given as single dose preoperatively.Pregabalin 150 mg  is given preoperatively, then 1 to 2 times/day postoperatively for 2 days. High preoperative pregabalin dose combined with a general anesthetic can result in sedation which can be lessened by limiting dose to less than 300 mg/day.              Alpha-2 agonists are sedating  with some  analgesic activity They attenuate hemodynamic response to pain and cause minimal respiratory depression. However side effects of hypotension and bradycardia may limit use of these agents. Clonidine improves analgesia and decreases opioid consumption when added to spinal and peripheral nerve blocks.The long  half-life of nine  hours limits intraoperative use. Dexmedetomidineismore potent and  has shorter half-life;.It decreases opioid use (and thus  nausea and vomiting)Ketamine-The site of action is mainlyN-methyl-d-aspartate (NMDA) receptors in spinal cord and brain .The NMDA receptor is  involved in development of opioid tolerance; blocking  the receptor slows and may reverse tolerance. It also decreases the windup and central sensitization  phenomena. which leads to the chronic pain state.This process is inhibited by blocking of the  NMDA receptor.A single bolus of ketamine (0.25-0.5 mg/kg)has been used.However an infusion started intraoperatively and continued postoperatively (0.15-0.5 mg/kg/hr is most effective.Higher doses may cause changes in mental status. It improves analgesia in patients who require large amounts of opiates or are opioid tolerant.IV lidocaine: has been utilized off-label for acute pain. It improves analgesia and decreases opioid consumption, .It shortens time to return of bowel function in colorectal, laparoscopic cholecystectomy, prostate, and possibly spinal surgeries; It has been found ineffective for orthopedic and gynecologic surgery.Steroids: have analgesic properties,antiemetic and antipyretic properties. They improve pain and recovery scores, well-being, and appetite after surgery and decrease opioid use.They have a delayed onset and a long duration of action .They may decrease incidence of chronic pain after surgery. They are avoided in patients with history of GI bleeding and  can cause increase in blood glucose.
Finally for the last two decades, these agents are usually not used in isolation but as part of a Multimodal or balanced regime. Multimodal analgesia here is defined as the achievement of improved pain relief through the synergistic or at least additive effects of different agents (with different mechanisms or  sites of action). This results in lower doses of the individual drugs and  enables a concomitant reduction in the side effects.
Role of Regional Anesthesia
Regional anesthesia, utilizing mainly local anesthetics, is the most effective method to attenuate the  metabolic response  to surgery.These include intrathecal routes,epidural routes and peripheral nerve blocks.
Multimodal combinations of drugs (usually local anesthetics and opioids) can be inserted into the intrathecal space. This  has the advantages of simplicity, reliability, and low-dose requirements. It has rapid onset and offset, easy administration, minimal expense, and minimal adverse effects or complications. But disadvantages are also present. Nausea and vomiting are often induced by neuraxial opioids, pruritus is significantly high and urinary retention is common.
The epidural route of drug delivery has achieved widespread use for surgical analgesia as it provides better pain relief than parenteral opioid administration. Epidural blockade is usually performed in the thoracic and lumbar regions, or caudally.  However, newer, studies seem to indicate  the benefits of epidural analgesia may not  be as significant as previously believed. Neuroaxial analgesic techniques have the potential for rare but very  serious adverse complications.The use of low molecular weight heparin for deep vein thrombosis prophylaxis increases  the risk of epidural hematoma .Due to a perceived unfavorable risk benefit ratio, the use of epidural techniques is generally decreasing although in some specific situations, they are still recommended.
Peripheral nerve blocks:  There is a huge upsurge in the incorporation of these techniques .They may allow avoidance of opioids, but can be combined with opioids and other analgesics; They are useful after both routine as well as ambulatory surgery;A few examples include supraclavicular  brachial plexus  block which provides excellent analgesia for upper extremity; the  interscalene approach can be used for the placement of continuous interscalene catheters or single-shot local anesthetic dosing for open shoulder surgeries and surgeries of the proximal upper extremity; paravertebral blocks are  used for breast surgery (may decrease incidence of recurrence of breast cancer) and for thoracotomies and VATs.The  improvement in respiratory mechanics same as with epidural vs patient-controlled analgesia (PCA); It can avoid hypotension and urinary retention which are common with eoidurals;transversus abdominis plane (TAP) block — useful especially  in  abdominal surgeries under general anesthesia without intrathecal or epidural narcotics; lower extremity  blocks — currently these are the mainstay of pain control after  knee and hip surgery.
Their  main disadvantage is that they are time consuming (delay start of surgery); Single shot blocks have a small but finite risk of complications like intravascular puncture ;their effect may not last long ;Placement of catheters with continuous infusions  can solve this problem but can also lead to toxicity 
 Advantages of nerve blocks include decreased use of opioids and most side effects; improved patient satisfaction; decreased time to discharge when combined with aggressive rehabilitation
A new paradigm in this field is the use of Ultrasound which has revolutionized regional anesthesia.Proficient anesthesiologists have success rates of close to 100%; US allows faster administration and onset, less patient discomfort, and   lower volumes of medication-which translates into increased patient safety.
There is an increasing trend towards tailoring analgesia to individual patient needs. One of the first ways this was done was by the use of  PCA-Patient Controlled analgesia.The PCA device is usually an electronic or mechanical pump , most often given to patients who  undergo moderate or major surgery and are expected to be in moderate to severe pain postoperatively. Background drug infusions run in parallel with predetermined selfadministered boluses once a  pre set“lockout” period has elapsed.These primarily use intravenous opioids  but other drugs and other routes             ( epidural, PNB catheters)can also be used.Besides  good pain relief PCA systems provide the patient with a considerable degree of autonomy and satisfaction.  In the future it may be possible to tailor analgesia further depending on the age, sex and especially the genomic background of the patient.
There is an increasing trend towards the use of enhanced clinical pathways which help in the recovery and rehabilitation of post operative patients .Good post operative pain management is an essential part of such pathways.
Anesthesiologists managing  post operative pain must be mindful of managing the analgesic gap-the term descrbes increased pain in the  period between immediate postoperative care and discharge on simple oral analgesia.  Three groups of patients are described :1. Those where the pain intensity is expected to decline rapidly- they are best managed by simple analgesics by oral route with provision for opioid supplementation with a rapidly acting drug if required 2. Those where the decline in pain intensity will occur over days to a week-Here  a baseline of slow-release opioid is given , with fast-acting oral opioid available on demand.3. Those where pain is thought to be stable but ongoing for longer periods of time-  conversion from parenteral to oral is done  using a conversion chart.    The use of infusion catheters for longer term use  may help the management of patients in the second and third  groups
All anesthesiologists are now  aware of the possibility of  developing Chronic pain after surgery: Over 50% of patients undergoing thoracotomy have pain 1 yr after surgery; significant long-term pain  is seen in other surgeries(inguinal hernias , breast surgery); poorly managed acute pain and development of chronic pain are  strongly linked ; small-scale studies show aggressive treatment of acute perioperative pain decreases incidence of chronic pain. The role of Pre-emptive or preventive analgesia  is however still controversial and studies have given conflicting results.Techniques of regional anesthesia ,perioperative use of gabapentinoids and NMDA antagonists might play a role. Besides this, minimally invasive surgery and providing good postoperative analgesia may also reduce the incidence of this complication.
To conclude Postoperative pain management today is being  is measured as a hallmark of the quality of care that is given to hospital patients and  the anesthesiologists knowledge of the art and science  of post operative pain management  makes an enormous impact on postoperative recovery and   long term well-being  of the patient .                             References.                                                                                                                            Apfelbaum JL et al: Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. AnesthAnal 2003Aug97;(2): 534-40
Buvanendran A, Kroin JS (2009) Multimodal analgesia for controlling acute postoperative pain. Curr Opin Anaesthesiol 22:588–593                                                        
White PF, Kehlet H (2010) Improving postoperative pain management: what are the unresolved issues? Anesthesiology 112:200–225                                                           
Wu CI, Raja SN: Treatment of postoperative pain. Lancet 2011;377:2215
Kehlet H, Jensen T, Woolf CJ (2006) Persistent postsurgical pain: risk factor and prevention. Lancet 367:1618–1625