Intraoperative Low-dose Ketamine Infusion as the Main Analgesic in Burn Patients
| Status: | Recruiting |
|---|---|
| Conditions: | Other Indications, Hospital |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 3/16/2019 |
| Start Date: | February 27, 2018 |
| End Date: | August 2020 |
| Contact: | Katharine Miles, MD |
| Email: | katharine.miles@lumc.edu |
| Phone: | 708-216-4174 |
The purpose of this study is to determine whether a low-dose ketamine infusion can be used as
the main intra-operative analgesic in different burn patients, and thereby reduce the total
intra-operative opioid requirement. Secondary objectives are to determine whether this
low-dose ketamine infusion will lengthen the amount of time to the first narcotic given in
the recovery room or ICU, and whether pain scores for awake patients will be lower
post-operatively.
the main intra-operative analgesic in different burn patients, and thereby reduce the total
intra-operative opioid requirement. Secondary objectives are to determine whether this
low-dose ketamine infusion will lengthen the amount of time to the first narcotic given in
the recovery room or ICU, and whether pain scores for awake patients will be lower
post-operatively.
Burn patients suffer from several types of pain (due to stimulation of mechanoreceptors,
nociceptors, and chemical stimulation) as well as other injuries. Multiple agents are used to
control pain in this special group. Due to different pain mechanisms and the up-regulation of
the mu receptors, numerous pain controlling modalities should be sought. Opioids are the
mainstay in treating pain in such patients. Adjuvant non-opioid agents are less effective if
used alone. These agents include non-steroidal, anti-inflammatory drugs (NSAIDs), α-2
antagonists, local anesthetics and ketamine. Regional blocks can be used in the perioperative
period if there are no contraindications, but catheters cannot be left in place for an
extended period of time. Opioids have many side effects such as respiratory depression,
nausea, vomiting, itching, urinary retention, and hyperalgesia. The latter is of concern in
any patient on chronic opioids, including burn patients.
Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) antagonist that has been
successfully used in burn intensive care units (BICUs) to provide pain for dressing changes.
It also has been in use in BICUs to supplement the analgesic effect of opioids. Ketamine
exerts its clinical analgesic effect mainly by NMDA antagonism, but it also interacts with
other receptors such as AMPA monoaminergic, nicotinic, muscarinic, and mu, delta, and kappa
opioid receptors. It resembles local anesthetics in its interaction with sodium channels. Low
dose ketamine infusion (LDKI) has been used as a postoperative analgesic in different
patients group for various duration of time. Some studies have shown some benefit to using
intraoperative low-dose ketamine in non-burn surgery in order to reduce post-operative opiate
requirement. Little is known, from the literature, if an intraoperative low-dose ketamine
infusion can be used as the main analgesic in burn patients in general, and in severely
burned patients in specific.
Previous studies have shown that ketamine potentiates the analgesic effects of low-dose
fentanyl and, to a lesser degree, low-dose morphine by stimulation of phosphorylated
extracellular signal-regulated kinase 1/2 (ERK1/2). It also increases the duration of
opioid-induced analgesia, delays opioid induced tolerance, and plays a role in preventing
opioid-induced hyperalgesia by delaying desensitization and by improving resensitization of
ERK 1/2 signaling. From this pharmacologic standpoint, it is advantageous over other pain
modalities in hemodynamically-compromised burn patients.
Ketamine is being used extensively in burn ICUs but the low-dose infusion of ketamine did not
capture as much attention in treating burn patients in the operating room (OR). Burn patients
come to the OR numerous times for wound debridement, skin grafting or unrelated surgeries.
The use of inhalation anesthetics poses the risk of hypotension in these hemodynamically
fragile patients. Opioids are still the main agents in treating such patients in the OR and
they are sometimes given in very high doses, due to the resistance and up-regulation of the
mu opioid receptors mentioned above. These doses are often not very effective in controlling
pain and can lead to hypotension if combined with potent inhalation agents.
nociceptors, and chemical stimulation) as well as other injuries. Multiple agents are used to
control pain in this special group. Due to different pain mechanisms and the up-regulation of
the mu receptors, numerous pain controlling modalities should be sought. Opioids are the
mainstay in treating pain in such patients. Adjuvant non-opioid agents are less effective if
used alone. These agents include non-steroidal, anti-inflammatory drugs (NSAIDs), α-2
antagonists, local anesthetics and ketamine. Regional blocks can be used in the perioperative
period if there are no contraindications, but catheters cannot be left in place for an
extended period of time. Opioids have many side effects such as respiratory depression,
nausea, vomiting, itching, urinary retention, and hyperalgesia. The latter is of concern in
any patient on chronic opioids, including burn patients.
Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) antagonist that has been
successfully used in burn intensive care units (BICUs) to provide pain for dressing changes.
It also has been in use in BICUs to supplement the analgesic effect of opioids. Ketamine
exerts its clinical analgesic effect mainly by NMDA antagonism, but it also interacts with
other receptors such as AMPA monoaminergic, nicotinic, muscarinic, and mu, delta, and kappa
opioid receptors. It resembles local anesthetics in its interaction with sodium channels. Low
dose ketamine infusion (LDKI) has been used as a postoperative analgesic in different
patients group for various duration of time. Some studies have shown some benefit to using
intraoperative low-dose ketamine in non-burn surgery in order to reduce post-operative opiate
requirement. Little is known, from the literature, if an intraoperative low-dose ketamine
infusion can be used as the main analgesic in burn patients in general, and in severely
burned patients in specific.
Previous studies have shown that ketamine potentiates the analgesic effects of low-dose
fentanyl and, to a lesser degree, low-dose morphine by stimulation of phosphorylated
extracellular signal-regulated kinase 1/2 (ERK1/2). It also increases the duration of
opioid-induced analgesia, delays opioid induced tolerance, and plays a role in preventing
opioid-induced hyperalgesia by delaying desensitization and by improving resensitization of
ERK 1/2 signaling. From this pharmacologic standpoint, it is advantageous over other pain
modalities in hemodynamically-compromised burn patients.
Ketamine is being used extensively in burn ICUs but the low-dose infusion of ketamine did not
capture as much attention in treating burn patients in the operating room (OR). Burn patients
come to the OR numerous times for wound debridement, skin grafting or unrelated surgeries.
The use of inhalation anesthetics poses the risk of hypotension in these hemodynamically
fragile patients. Opioids are still the main agents in treating such patients in the OR and
they are sometimes given in very high doses, due to the resistance and up-regulation of the
mu opioid receptors mentioned above. These doses are often not very effective in controlling
pain and can lead to hypotension if combined with potent inhalation agents.
Inclusion Criteria:
- All adult burn patients aged 18-80 presenting to the operating room, both intubated
and non-intubated
- Patients having a procedure performed in Russo operating rooms at Loyola University
Medical Center
Exclusion Criteria:
- Allergy to ketamine or benzodiazepines
- Ketamine use in the preceding 24 hours
- Children (patients under age 18), prisoners, pregnant or breastfeeding women, patients
with psychosis, patients with developmental delay, and any condition which, in the
opinion of the investigator, would prevent full participation in this study or would
interfere with the evaluation of the trial endpoints.
- Increased intracranial pressure at the discretion of the investigator
- Increased intraocular pressure at the discretion of the investigator
- Porphyria at the discretion of the investigator
- Thyroid disorders at the discretion of the investigator
We found this trial at
1
site
2160 South 1st Avenue
Maywood, Illinois 60153
Maywood, Illinois 60153
(888) 584-7888
Phone: 708-216-4174
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