Ketolorac Versus Saline at Laparoscopic Incision Sites

As the push for more minimally invasive and economical procedures increases, special
attention will be paid to reasons why patients experience complications, unanticipated
outpatient visits or require prolonged recovery times or even unplanned hospital admissions.
Insufficient pain control is one of the prime reasons for increased level of care (16, 17),
with pain defined as a "conscious unpleasant sensory and emotional experience associated
with actual or potential tissue damage" (12). Appropriate pain control may advantageously
affect length of hospital stay and related expense, decrease chronic pain syndromes, improve
patient experience and result in fewer complications in the postoperative period (12).

Multiple methods of analgesia are employed to improve pain control after procedures,
including intravenous medications, regional anesthesia and local injections (12, 16, 17).
Laparoscopic procedures typically involve general anesthesia, and in an effort to improve
recovery in the post anesthesia care unit (PACU) anesthesiologists employ shorter acting
agents (2). Patients who received short acting anesthetic agents were more likely to bypass
the PACU, particularly patients undergoing gynecologic surgery (2). This does not alleviate,
and in fact may intensify, the need for adequate pain control in the immediate postoperative
period.

Several strategies have been tested in an effort to improve analgesia in this critical time
period, including intravenous, regional and local anesthesia (12). Multiple types of pain
medications have been used to improve postsurgical pain. Opioids are commonly used, however
may be associated with multiple negative affects including nausea and vomiting, delayed
gastric emptying, sedation and respiratory depression (12). Postoperative nausea and
vomiting, pain control and drowsiness were all factors contributing to prolonged recovery
room stays (15). Other medications may be used to decrease opioid consumption, even the most
common analgesics. Acetaminophen has been found to decrease opioid requirements
postoperatively up to 20% (12). Postoperative NSAID use is quite common (12). With respect
to NSAIDs in particular, ketorolac has been utilized due to its ability to improve pain
control and lessen the amount of opioid medication given (12). Ketorolac offers advantages
over opioids, particularly with respect to avoidance of and decrease in opioid associated
side effects (4). These advantages have implications for both patient comfort and length of
hospital stay following surgery. The use of adjunct non-opioid medications may lead to
shorter PACU stays, decreased discharge times and fewer adverse effects such as respiratory
depression and postoperative nausea and vomiting (4, 5, 15). Cassinelli et al demonstrated
improved pain control when using IV ketorolac following lumbar decompression surgery,
showing patients had decreased morphine requirements with improved pain scores following
surgery. Coloma et al compared intravenous versus local ketorolac versus normal saline
following anorectal surgery and found use of ketorolac in any form decreased pain scores.
This was clinically significant in that it decreased the requirement for oral pain
medications without a concomitant increase in side effects or complications. That group
found that although both IV and local ketorolac provided pain relief following surgery, only
local administration gave statistically significant lower pain scores on arrival to the PACU
and had a shorter time to discharge compared to controls. In addition, a study by Ben-David
found administration of 30 mg ketorolac locally had improved pain scores than when 60 mg was
given intramuscularly (22). A comparison during orthopedic surgery of local vs systemic
administration of ketorolac showed improved pain scores with local administration (23).
These beneficial findings were in no way universal. Kardash et al compared ketorolac use in
patients undergoing hernia repair and found no difference in pain levels postoperatively
whether patients had ketorolac injected either at the site of the incision or peripherally
(in this case a subcutaneous injection in the contralateral abdominal wall). These findings
were mitigated somewhat due to lack of a control group, omitted primarily because the
authors felt NSAIDs were a routine part of postoperative pain control and could not be
ethically withheld. Ketorolac does have drawbacks in the form of suspected hematologic
impact affecting platelet aggregation and bleeding time and must be used with cautiously in
patients with renal compromise (12).

The source of pain is multifactorial, including not only intra-abdominal discomfort from the
procedure itself but also from the skin incision as well (3). Multiple studies have compared
local anesthesia injected at the site of laparoscopic incision to a normal saline control.
Khaira et al examined normal saline vs. bupivacaine injections at the surgical incision site
early in surgery and found a decrease in parenteral opioid use in patients who received the
anesthetic injection. Cansino et al compared oral NSAID combined with a lidocaine
paracervical block to oral placebo and a paracervical block that included both lidocaine and
ketorolac during first trimester surgical abortion. They found improved pain control with
the combined paracervical block particularly during cervical dilation, although the
remaining pain scores were not significantly different. Mohair et al examined the effects of
infiltration with pain medication in postoperative pain control in patients undergoing
breast augmentation. They did this by infiltrating normal saline, ketorolac, bupivacaine or
both ketorolac and bupivacaine into the breast pocket following dissection. Their results
suggested the combined medication improved pain levels immediately postoperative and through
the time of discharge at their outpatient surgery center. Each pain medication alone also
improved pain scores although to a lesser extent. It is unclear if the statistical
significance translates to a clinical significance. A follow up to the initial study of pain
medication infiltrated into breast pockets in breast augmentation followed longer term pain
scores in postoperative patients who had either normal saline or the combination ketorolac
and bupivacaine infiltrated during surgery. Results showed improved pain scores over the
first five postoperative days as determined by the visual analogue scale and amount of pain
medication used when the analgesic solution was infiltrated during surgery. Again, it
remains unclear whether this is clinically significant, as the amount of pain medication
utilized differed by approximately one to two tablets daily. Mahabir et al theorized the
possible benefit of ketorolac over bupivacaine could stem from the difference in pKa in the
two medications. The pKa of ketorolac is 3.5, indicating a higher activity in acidic
tissues, such as those that are damaged and inflamed, relative to a medication such as
bupivacaine with its more basic pKa of 8.1 (16).

Not only is the type of analgesia in question but also the timing in administration:
preincisional vs. at surgical closure. Einarsson et al specifically investigated local pain
control in laparoscopic port sites using patients as their own controls. This study compared
pain control in patients with bupivacaine and normal saline infiltrated at port sites, using
each patient as their own control and found postoperative administration of bupivicaine
resulted in better pain control. Ke et al examined efficacy of pain control with respect to
both medication administered as well as timing when they compared infiltration of wounds
with either bupivacaine or normal saline before initial incision or at incision closure. The
results indicated pre-incision injection provided better pain control with longer lasting
analgesic effects, however the study was limited by a small sample size leading to possibly
less significant results. Lam et al also investigated local pain control at laparoscopic
port sites with a placebo controlled trial using either lignocaine or normal saline at the
initial incision or at closing the case. Their results advocated for using analgesia at the
time of closure, showing decreased pain scores for up to 24 hours postoperatively in that
group, and only minimal improvement with preemptive analgesia. These results may not be
clinically significant because despite the decreased pain scores, amount of pain medication
utilized was the same. Despite some studies indicating improved pain control with local
anesthesia, multiple randomized, placebo controlled, double blind studies have not shown any
significant difference between saline and bupivacaine with respect to post operative pain
(18-21).

Inclusion Criteria:

- Female undergoing gynecologic laparoscopic surgery

- Surgeries less than 60 minutes

Exclusion Criteria:

- Patients with a diagnosis of stage III or IV endometriosis, chronic pelvic pain,
chronic narcotic use, allergy to anesthetics, contraindication to ketolorac

- Robotic assisted procedures, single-port laparoscopy or conversion to laparotomy