Ileus seems an almost unavoidable side effect of most types of bowel surgery. This is
unfortunate, since postoperative ileus is not only unpleasant for the patient, but also has
detrimental effects on recovery from surgery. The maintenance of enteral nutrition has been
shown to be an important factor in ensuring rapid recovery from gastrointestinal surgery, as
the catabolic state decreases immune function, delays wound healing, and increases morbidity.
However, ileus often precludes enteral feeding. As a result, duration of postoperative ileus
is frequently a major determinant of duration of hospitalization. At this time, the most
effective manner to minimize the duration of postoperative ileus is the use of continuous
local anesthetic epidural analgesia 3 as confirmed by a systematic review on the topic. This
effect appears specifically related to the use of local anesthetic, as postoperative epidural
administration of opiates alone is without effect on ileus.
Postoperative ileus is largely inflammatory in origin, and appears to be reduced when
surgical techniques (e.g. minimally invasive approaches) are used that are associated with
less inflammatory responses (as determined from interleukin-6 and C-reactive protein levels).
The observation that non-steroidal anti-inflammatory drugs are effective in reducing the
duration of ileus supports this hypothesis (but these are often avoided because of concern
for bleeding).
Taken together, these findings suggest that epidural analgesia with local anesthetics may
shorten the duration of postoperative ileus because of an anti-inflammatory action of the
local anesthetic. Modulating effects of local anesthetics on the inflammatory system are well
known, and have been described in vitro, in animal studies, and to a lesser extent in
clinical trials. In animals, inflammatory-mediated injury in heart is ameliorated by local
anesthetics, as is endotoxin- or acid-mediated lung injury. In humans, thrombosis incidence11
and hypercoagulation after surgery (both inflammatory-mediated processes) are decreased by
systemic local anesthetics (yet physiologic coagulation is not affected). Important in the
current context, the effectiveness of local anesthetics in the setting of inflammatory bowel
disease is well established. The compounds have been shown to decrease the release of
inflammatory mediators from neutrophils, which may play a role in this beneficial effect. As
another example, cognitive deficits after cardiac surgery probably result from a combination
of emboli and the inflammatory response that these induce in the brain. Systemic local
anesthetics would be expected to interfere with both of these processes, and indeed improve
cognitive outcome in this setting.16 The mechanism behind this action is most likely a
modulatory effect of local anesthetics on neutrophils. Local anesthetics have been shown to
inhibit neutrophil priming (a critical component of neutrophil-mediated tissue injury), but
not to interfere with activation (required for wound healing and host defense). Importantly,
and in contrast to classic inflammatory suppression, this inflammatory modulation by local
anesthetics is therefore not associated with detrimental effects on wound healing and
infection rates. We have shown that selective inhibition by local anesthetics of cellular Gq
proteins explains this effect. Other effects, including those on mediator release, may also
play a role. Since epidural anesthesia leads to significant blood levels of local anesthetics
(1 to 5 µM), it is conceivable that the inflammatory modulatory action of systemically
absorbed local anesthetic explains the beneficial effects of epidural analgesia on duration
of postoperative ileus. An additional beneficial effect on return of bowel function will
result from the reduced requirement for opiate analgesics.
If this is the case, then a similar beneficial effect might be obtained using systemic
administration of local anesthetics. Both the inflammatory modulatory effects and the
analgesic actions (thereby decreasing opiate requirements) are present when these drugs are
given intravenously. This approach would have significant advantages over epidural
administration. The common use of perioperative anticoagulation for the prevention of deep
venous thrombosis has made appropriate timing of epidural placement and removal considerably
more difficult. Epidural placement and management costs time and adds expense. Many patients
may not desire the placement of an epidural catheter. In addition, the uncommon but real
risks of epidural placement (certainly in the thoracic region) would be avoided by systemic
administration of the local anesthetic. The major risks are epidural hematoma or abscess,
both of which can be devastating.
Several clinical trials indicate that systemic local anesthetics have beneficial actions on
the return of bowel function after surgery. In patients undergoing radical prostatectomy,
administration of lidocaine (3 mg/min) for the duration of surgery and 1 h postoperatively
resulted in a 1 day earlier return of bowel function and an associated earlier discharge from
the hospital as compared with placebo. Significantly earlier return of propulsive motility in
the colon was also observed in patients undergoing cholecystectomy who received intravenous
lidocaine (3 mg/min intraoperatively and continued 24 h post surgery). Similarly,
intraoperative instillation of bupivacaine demonstrated beneficial effects on colonic
motility.
However, no study has investigated the effect on postoperative bowel function of systemically
administered local anesthetic after bowel surgery. It is in this setting that restoration of
bowel function is most relevant. We hypothesize that intravenous, intraoperative and
postoperative administration of local anesthetic, added to patient-controlled analgesia (PCA)
for post-operative pain relief, will result in more rapid return of bowel function as
compared with PCA alone. This hypothesis will be tested in a randomized, blinded, controlled
clinical trial in patients undergoing open colectomy for tumor.