Acute Postoperative Pain Flashcards
Chronic persistent postsurgical pain (CPSP) is relatively common after procedures such as …
limb amputation (30%-83%), thoracotomy (22%-67%), sternotomy (27%), breast surgery (11%-57%), and gallbladder surgery (up to 56%)
Acute Effects of postoperative pain
Transmission of nociceptive stimuli from the periphery to the CNS results in the neuroendocrine stress response, a combination of local inflammatory substances (e.g., cytokines, prostaglandins, leukotrienes, tumor necrosis factor-α) and systemic mediators of the neuroendocrine response. The dominant neuroendocrine responses to pain involve hypothalamic-pituitary-adrenocortical and sympathoadrenal interactions. Suprasegmental reflex responses to pain result in increased sympathetic tone, increased catecholamine and catabolic hormone secretion (e.g., cortisol, adrenocorticotropic hormone, antidiuretic hormone, glucagon, aldosterone, renin, angiotensin II), and decreased secretion of anabolic hormones. The effects
include sodium and water retention and increased levels of blood glucose, free fatty acids, ketone bodies, and lactate.
A hypermetabolic, catabolic state occurs as metabolism and oxygen consumption are increased and metabolic substrates are mobilized from storage depots
The neuroendocrine stress response may enhance detrimental physiologic effects in other areas of the body. The stress response is likely a factor in the postoperative development of hypercoagulability. Enhancement of coagulation (i.e., decreased levels of natural anticoagulants and increased levels of procoagulants), inhibition of fibrinolysis, and increased platelet reactivity and plasma viscosity may enhance the incidence of postoperative hypercoagulable- related events such as deep venous thrombosis, vascular graft failure, and myocardial ischemia. The stress response may also enhance postoperative immunosuppression, the extent of which correlates with the severity of surgical injury. Hyperglycemia from the stress response may contribute to poor wound healing and depression of immune function.
Sympathetic activation may increase myocardial oxygen consumption, which may be important in the development of myocardial ischemia and infarction, and may decrease myocardial oxygen supply through coronary vasoconstriction and attenuation of local metabolic coronary vasodilation. Activation of the sympathetic nervous system may also delay return of postoperative gastrointestinal motility, which may develop into paralytic ileus.
Nociceptors are activated after surgical trauma and may initiate several detrimental spinal reflex arcs. Postoperative respiratory function is markedly decreased, especially
after upper abdominal and thoracic surgery. Spinal reflex inhibition of phrenic nerve activity is an important component of this decreased postoperative pulmonary function
NSAID mechanism of action and mechanisms of side effects
The primary mechanism by which NSAIDs exert their analgesic effect is through inhibition of cyclooxygenase (COX) and synthesis of prostaglandins, which are important mediators of peripheral sensitization
and hyperalgesia. In addition to being peripherally acting analgesics, NSAIDs can also exert their analgesic effects through inhibition of spinal COX. The discovery of at least two COX isoforms (i.e., COX-1 is constitutive and COX-2 is inducible) with different functions (i.e., COX-1 participates
in platelet aggregation, hemostasis, and gastric mucosal protection, whereas COX-2 participates in pain, inflam- mation, and fever) has led to the development of selective COX-2 inhibitors that differ from traditional NSAIDs, which block both COX-1 and COX-2.
Perioperative use of NSAIDs has several side effects, including decreased hemostasis, renal dysfunction, and gastrointestinal hemorrhage. Inhibition of COX and the formation of prostaglandins cause many of the side effects, which mediate many diverse processes throughout the
body. Decreased hemostasis from NSAID use is from platelet dysfunction and inhibition of thromboxane A2 (generated by COX-1), an important mediator of platelet aggregation and vasoconstriction.
Does NSAIDs affect the ossification process?
Whether NSAIDs may also have a deleterious effect on bone healing and osteogenesis is controversial. Although NSAIDs have been used following acetabular/hip fractures and hip replacement surgery to reduce heterotopic ossification, the short-term effect of NSAIDs on other skeletal tissues is less clear. Two recent systematic reviews indicated that when examining the highest-quality studies, there was no increased risk of nonunion with NSAID exposure. Certainly, a short-term NSAID regimen can be used for treatment of post-fracture pain without significantly increasing the risk of disrupted healing. A brief (<14 days) exposure
to normal-dose NSAIDs (e.g., ketorolac <120 mg/day) was safe after spinal fusion; however, use of large-dose ketorolac (>120 mg/day) increased the risk of nonunion, suggesting a dose-dependent effect of perioperative NSAIDs on spinal fusion healing. Spine surgeons will more commonly err
on the conservative side and refuse to have postoperative spine fusion patients receive NSAIDs
Are COX-2 inhibitors contraindicated for the treatment of perioperative pain?
The perioperative use of potent COX-2 inhibitors resulted in a higher rate of cardiovascular events in high-risk (coronary artery bypass grafting) but not lower-risk (major noncardiac surgery) patients. Celecoxib, a COX-2
inhibitor, has less COX-2 selectivity than other more potent COX-2 inhibitors (rofecoxib) and is still clinically available. Nissen and associates conducted a randomized controlled trial (RCT) of 24,081 patients randomly assigned to celecoxib, naproxen, or ibuprofen and found that celecoxib
was noninferior to ibuprofen or naproxen with regard to cardiovascular safety. Liu and associates studied 10,873 patients admitted for total joint arthroplasty and concluded that perioperative use of NSAIDs was not associated with increased risk of postoperative myocardial ischemia and
may reduce the hospital length of stay
Mechanism of action of Acetaminophen
Acetaminophen has antipyretic and antiinflammatory properties. Its mechanism of action is through activation of descending serotonergic pathways in the CNS and via the inhibition of prostaglandin synthesis
Mechanism of action Gabapentinoids
Gabapentin and pregabalin, antiepileptic drugs also used in the treatment of neuropathic pain, interact with calcium channel α2-delta ligands to inhibit calcium influx and subsequent release of excitatory neurotransmitters.
Mechanism of action of tamadol
Tramadol is a synthetic opioid consisting of (+) and (−) enantiomers that contribute to the analgesic activity via different mechanisms. The (+) enantiomer of tramadol is an opioid µ-receptor agonist that also stimulates serotonin release and inhibits its re-uptake, whereas the (−) enantiomer inhibits norepinephrine re-uptake
