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Page 6 of 13 Gharagozloo. Mini-invasive Surg 2020;4:8 I http://dx.doi.org/10.20517/2574-1225.2019.62

onset, they also have shortened duration of action and prolonged use can lead to a “roller coaster” effect
of pain followed by relief of pain. Opioids are associated with significant side effects: nausea, vomiting,
respiratory compromise, and ileus. Consequently, they are used in a manner which can result in ineffective
pain control.

Oral administration is reserved for when the patient can take a diet without difficulty. Transitioning
smoothly to an oral regimen is key. A shortcoming of the oral route is the delay in the onset and peak
of drug activity. The addition of a long acting opioid will aid in preventing this “peak and valley”
phenomenon.

The use of opioids may extend for several days to several weeks and is highly patient dependent. Many
practitioners are hesitant to prescribe opioids long term for several reasons. The treatment of pain with
opioids and the prevention of the side effects is preferable to the consequences associated with poor pain
control, usually stated as side effects of nausea and constipation as well as fear of addiction. All prescribers
of opioids have an ethical duty to provide appropriate pain relief to their patients, while taking into account
the many societal and political issues that have emerged as the result of opioid over prescription. Obviously,
opioids need to represent an adjunct to a more effective pain management strategy.

Nonsteroidal anti-inflammatory agents
Inflammation is a natural and often protective response to tissue injury caused by surgery. It usually
subsides when healing is complete. Inflammation is triggered by the release of chemical mediators, which
progress with a cascade effect. Prostaglandins are key mediators in the process of nociception. Prostaglandins
are synthesized in the spinal cord and are produced from arachidonic acid via the cyclooxygenase pathway.
[2]
There are two defined and a third as yet undefined cyclooxygenase enzymes . COX-1 is in most cells
as well as the peripheral and central nervous systems and is produced a number of pathways. COX-2 is
generated to a more limited extent, mostly in the central nervous system. Inhibiting the COX enzyme and
thereby decreasing peripheral and central prostaglandin production has been shown: (1) to decrease the
inflammation associated with tissue injury; and (2) to decrease peripheral and central sensitization. Zhu
[16]
and Eisenach demonstrated that there are differences in spinal COX isoenzymes involved in different
pain states, with a dominant role for spinal COX-2 with peripheral inflammation and a more exclusive role
for COX-1 after incisional surgery. This may have implications for control of hypersensitivity after nerve
injury but needs to be shown in humans.

Postoperative use of NSAIDs has been shown to decrease opioid use while still providing adequate
analgesia. Furthermore, NSAIDs have little effect on homodynamic parameters, with negligible changes in
blood pressure and stroke volume. In addition, in comparison to opioids such as morphine, which has been
shown to decrease minute ventilation and increase pulmonary vasoconstriction, NSAIDs have very little
[2]
effect on pulmonary circulation .
The use of NSAIDs may impact renal function. This is especially relevant in thoracic surgical patients
who are usually elderly and are subjected to postoperative fluid restriction. However, several studies have
not supported this hypothesis. In patients with normal preoperative renal function undergoing thoracic
surgery, the use of NSAID was associated with minimal reduction in creatinine clearance and no change
in urine output . Another concern is the potential for gastrointestinal bleeding associated with NSAID
[2]
use. While gastrointestinal erosion can be seen with long-term or chronic NSAID use, its incidence has not
been proven with short-term perioperative use. However, several studies have shown that, for long-term
[2]
use, COX-2 inhibitors may be superior to non-selective NSAID .

Ketorolac (Toradol), 15 mg every 6 h (can be intravenously or intramuscularly), is typically the NSAID
used in the perioperative period. The intravenous route is a preferred route in the immediate postoperative