Clinical Trial of Gabapentin to Improve Postoperative Pain in Surgical Patients
| Status: | Completed |
|---|---|
| Conditions: | Post-Surgical Pain |
| Therapuetic Areas: | Musculoskeletal |
| Healthy: | No |
| Age Range: | 65 - Any |
| Updated: | 4/21/2016 |
| Start Date: | January 2006 |
| End Date: | July 2014 |
This will be a double blind, placebo-controlled study of patients ≥65 years of age
undergoing surgery of the spine, hips and knees replacement at the University of California,
San Francisco (UCSF) Medical Center. Intraoperative anesthetic and postoperative pain
management will be standardized. Patients will be randomized to receive either placebo or
gabapentin preoperatively, and continued postoperatively until discharge. Intraoperative
anesthetic and other postoperative pain management strategies will be standardized.
Postoperative delirium will be measured using structured interviews. Cognitive function will
be measured using a battery of neurocognitive tests pre- and post-operatively. Using an
intention to treat strategy, we, the researchers at UCSF, will compare the amount of
postoperative pain, narcotic requirements, and postoperative delirium and cognitive
dysfunction between the two groups.
undergoing surgery of the spine, hips and knees replacement at the University of California,
San Francisco (UCSF) Medical Center. Intraoperative anesthetic and postoperative pain
management will be standardized. Patients will be randomized to receive either placebo or
gabapentin preoperatively, and continued postoperatively until discharge. Intraoperative
anesthetic and other postoperative pain management strategies will be standardized.
Postoperative delirium will be measured using structured interviews. Cognitive function will
be measured using a battery of neurocognitive tests pre- and post-operatively. Using an
intention to treat strategy, we, the researchers at UCSF, will compare the amount of
postoperative pain, narcotic requirements, and postoperative delirium and cognitive
dysfunction between the two groups.
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 elderly patients
undergoing surgery of the spine.
Aims
1. To compare the incidence of postoperative delirium and cognitive dysfunction between
the placebo vs. the gabapentin groups
2. To compare the amount of postoperative pain between the placebo vs. the gabapentin
groups
3. To compare the amount of narcotic used postoperatively between the placebo vs. the
gabapentin groups
Objectives
1. The broad overall goal is to identify the pathophysiology of postoperative delirium and
cognitive dysfunction in older patients
2. To determine whether optimization of postoperative pain control will reduce the
incidence of postoperative delirium and cognitive dysfunction
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 elderly patients
undergoing surgery of the spine.
Aims
1. To compare the incidence of postoperative delirium and cognitive dysfunction between
the placebo vs. the gabapentin groups
2. To compare the amount of postoperative pain between the placebo vs. the gabapentin
groups
3. To compare the amount of narcotic used postoperatively between the placebo vs. the
gabapentin groups
Objectives
1. The broad overall goal is to identify the pathophysiology of postoperative delirium and
cognitive dysfunction in older patients
2. To determine whether optimization of postoperative pain control will reduce the
incidence of postoperative delirium and cognitive dysfunction
Inclusion Criteria:
- Male or female ≥45 years of age undergoing surgery involving the spine, hip or knee
replacement.
- English speaking.
- Anticipated to stay in the hospital for at least 48 hours.
Exclusion Criteria:
- Patients who take gabapentin preoperatively, or have known sensitivity to the drug,
or those unable to be randomized to receive gabapentin.
- Subjects who are unable to provide informed consent.
- Patients with a history of narcotic tolerance.
- Patients with planned two stage spinal procedures (anterior-posterior spinal fusion
to be done on two separate days).
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