Postoperative delirium is a common condition, occurring in 10-70% of surgical patients after
major surgery. To date, few studies have examined events in the postoperative period as
contributing factors to postoperative delirium. We recently completed a study in over 500
geriatric surgical patients to examine whether the mode of postoperative analgesia delivery,
medication types, and the severity of postoperative pain may impact the occurrence of
postoperative delirium. In this study, 46% of patients developed postoperative delirium on
either the first or second postoperative day. By multivariate logistic regression, variables
which had independent association with postoperative delirium included age ≥80 years,
moderate to severe preoperative resting pain, and increased level of resting pain
postoperatively in comparison with preoperative baseline. When the analysis was focused on
patients who used Patient Controlled Analgesia (PCA) alone for postoperative pain control,
the amount of narcotic used (hydromorphone) was significantly higher in those with
postoperative delirium as compared to those without, suggesting that inadequate pain control
and/or the central effects of opioids may be associated with postoperative delirium. Since
increasing the doses of opioids in the elderly patients will likely lead to unwanted side
effects such as respiratory depression, the addition of a non-opioid agent may result in a
narcotic-sparing effect, and also reducing pain postoperatively.
Gabapentin is a structural analog of gamma-amino butyric acid, and has been used as an
anti-convulsant and anti-nociceptive drug. It is not metabolized in humans (therefore no
hepatic enzyme induction), and is eliminated from the body by renal clearance. In animal
studies, gabapentin has been demonstrated to be effective in reducing both allodynia and
hyperalgesia, and may have selective effect on the nociceptive process involved in central
sensitization. Gabapentin has been successfully used in the treatment of neuropathic pain and
other painful conditions. Recently, there is substantial evidence to suggest that gabapentin
also may be useful in the treatment of postoperative pain. To date, there have been nine
randomized clinical trials of gabapentin versus placebo including a total of over 700
patients. Taken together, these studies reported that gabapentin given perioperatively
significantly reduced postoperative analgesic requirements, and had minimum side effects. The
only reported significant side effects in these trials were mild sedation in two studies. In
patients with epilepsy, gabapentin can be introduced at therapeutic doses, and presents no
safety or serious side effect issues. Since gabapentin has negligible protein binding, it has
no interactions with other medications. It is recommended that metabolic and laboratory
monitoring is not necessary, and excellent cognitive profile is evident. At UCSF, gabapentin
has been used safely in a relatively large number of patients on an empiric bases in the
postoperative period, typically in surgical patients with substantial chronic pain, and more
recently, in patients who have undergone spinal surgery as an adjuvant agent to narcotics to
relieve postoperative radicular pain (personal communication with Peter Koo, Clinical
Pharmacist at UCSF). Typically, patients are started on gabapentin 300 mg po TID on the first
day, rapidly escalating to 600 mg TID on the second day, and finally to 900 mg TID the third
day until discharge. The UCSF experience suggests that gabapentin is well tolerated with
minimal side effects.
Hypothesis
We hypothesize that intensive pain management postoperatively using an adjuvant agent,
gabapentin, will lead to a decrease in the amount of postoperative pain experienced, thereby
resulting in a decrease in the incidence of postoperative delirium in older patients
undergoing noncardiac surgery.
Our specific aims were to: 1. Assess whether the administration of gabapentin was associated
with decreased occurrence of delirium, 2. Determine the extent to which gabapentin-associated
reductions in pain and/or opiate use reduced the occurrence of delirium, and 3. Determine
whether the administration of gabapentin was associated with shorter hospital stays. We
hypothesized that intensive pain management postoperatively using an adjuvant agent,
gabapentin, would lead to a decrease in the amount of opioids received, a decrease in
postoperative pain experienced, thereby resulting in a decrease in the incidence of
postoperative delirium.