Comparing Ketamine and Morphine in the Treatment of Acute Fracture Pain
| Status: | Recruiting |
|---|---|
| Conditions: | Chronic Pain, Orthopedic |
| Therapuetic Areas: | Musculoskeletal, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/25/2016 |
| Start Date: | April 2015 |
| End Date: | March 2017 |
| Contact: | Evan Schwarz, MD |
| Email: | schwarze@wusm.wustl.edu |
| Phone: | 3143629177 |
Comparing the Effectiveness of Low-dose Ketamine With Morphine to Treat Pain in Patients With Long Bone Fractures
Opioid pain medications such as morphine and dilaudid are commonly used in emergency
departments to treat pain in patients. Physicians are familiar with the side effects of
these medications; the most concerning of which is slowing or stopping a patient's
breathing, as well as dangerously lowering their blood pressure. An alternative medication
is ketamine. This medication is also commonly used in the emergency department, although it
is typically used to help sedate patients for uncomfortable procedures. Ketamine has also
been used for pain control, but in a much lower dosage that does not sedate patients. When
used for analgesia, it has typically been administered in combination with opioid pain
medications. To date, there is no study that looks at the effectiveness and safety of using
a low dose ketamine alone in comparison to the use of morphine. The purpose of this study is
to measure how well low-dose ketamine treats pain compared to morphine and to look at how
often serious side effects are seen with each medication.
departments to treat pain in patients. Physicians are familiar with the side effects of
these medications; the most concerning of which is slowing or stopping a patient's
breathing, as well as dangerously lowering their blood pressure. An alternative medication
is ketamine. This medication is also commonly used in the emergency department, although it
is typically used to help sedate patients for uncomfortable procedures. Ketamine has also
been used for pain control, but in a much lower dosage that does not sedate patients. When
used for analgesia, it has typically been administered in combination with opioid pain
medications. To date, there is no study that looks at the effectiveness and safety of using
a low dose ketamine alone in comparison to the use of morphine. The purpose of this study is
to measure how well low-dose ketamine treats pain compared to morphine and to look at how
often serious side effects are seen with each medication.
Opioid analgesia is the standard of care for treating moderate to severe pain in the
emergency department. It is an effective medication that most practitioners are familiar
using. Opioid use is not without risk, however. In managing acute pain, patients may
experience hypotension, respiratory depression, hypoxia, nausea and vomiting, dysphoria, and
itching. Patients at risk for respiratory depression include those with advanced age, renal
failure, or treated with multiple other sedatives.
The current recommended dose for opioid administration for acute pain management is
approximately 0.1 mg/kg as a loading dose, although some sources recommend up to 10 mg for
patients weighing more than 50 kg. (Ducharme 2011; Yak 2011) A single center study
demonstrated that patients received an average of 0.08 mg/kg of morphine, which did not
adequately control their pain; no patient received an initial dose of 10 mg.(Bijur 2012) A
post-operative pain study demonstrated that patients needed on average 12 mg or a mean
weight-based dose of 0.17 mg/kg of morphine to achieve an acceptable level of pain reduction
as determined by a 30 mm change on a visual analog scale.(Aubrun 2003) As such even if
patients received 1 mg of hydromorphone, their pain would still not be adequately
controlled.
Ketamine is a dissociative anesthetic that is a noncompetitive antagonist of
N-methyl-D-aspartate (NMDA) receptors. Low dose ketamine (LDK) (0.03-0.05 mg/kg) has
analgesic properties by modulating opioid tolerance and hyperalgesia.(Uprety 2013)
Currently, ketamine is used in the emergency department for moderate sedations and "awake"
intubations. In the pre-hospital setting, it is used in the management of patients with
excited delirium and pain control.(Keseg 2014)(Wiel 2014)(Jennings 2013) Benefits include
fewer serious adverse effects, especially involving respiratory depression and hypotension
which occurs with high-dose or repeat doses of opioids.(Jennings 2013) In addition to not
causing hypotension, ketamine can elevate a patient's blood pressure, which may be useful in
some circumstances.(Johansson 2009) Emergence delirium is associated with ketamine; this is
a rare adverse event and is usually alleviated with benzodiazepines. Additionally, LDK is
unlikely to cause the emergence delirium or the dissociation usually associated with larger
doses. Another potential complication is laryngospasm. Fortunately, this too is rare and in
most cases, patients are easily bagged through the event.
LDK is efficacious in reducing multiple types of pain in a variety of settings. Ketamine
infusions can reduce pain from vaso-occlusive pain crises seen in patients with sickle cell
anemia.(Uprety 2013)(Neri 2013)(Jennings 2013) In the postoperative setting and intensive
care unit, ketamine reduced the amount of morphine required to control pain.(Galinski
2007)(Bell 2006)(Herring 2013) In out-of-hospital trauma patients, ketamine combined with
morphine produced superior analgesia to morphine alone. All patients received morphine and
were then randomized to receive either morphine or ketamine if further analgesia was
required. Ketamine had a change in the visual analog scale (VAS) of -5.6 (CI -6.2 to -5.0)
while morphine had had a change of -3.2 (CI -3.7 to -2.7).(Jennings 2012) In another
pre-hospital study, ketamine was administered to 1030 patients for pain or anesthesia. No
patients incurred ketamine-induced respiratory adverse events.(Bredmose 2009) Preliminary
studies have also investigated LDK in the emergency department (ED). Available research
mainly consists of retrospective or observational data. In an observational study performed
in an urban ED in California, LDK significantly improved patient's pain without adversely
effecting blood pressure, heart rate, or respiratory drive. Twenty-four patients over age 18
who received ketamine for any reason were included. Three received ketamine for sedation
while the rest received it for analgesia. Most patients received opioids prior to receiving
ketamine, although the opioids did not result in improved pain scores. On a scale of 0 to
10, ketamine reduced pain from 8.9 ± 2.1 to 3.9 ± 3.4 (p<0.0001).(Richards 2013) In another
observational, ED based study, ketamine used as an analgesic was investigated. Thirty
patients with a variety of painful complaints (abdominal pain, back pain, nephrolithiasis,
biliary pain, fractures, sickle cell pain) were enrolled. Patients were initially
administered a combination of hydromorphone 0.5 mg and ketamine 15 mg with rescue doses of
hydromorphone 1 mg available 15 minutes and 30 minutes after the initial dose of analgesia.
In 28 patients (93%), there was a clinically significant decrease of 2 or more points on a
numerical rating score measured after the initial administration; 14 patients reported pain
scores of 0. Fourteen patients refused any additional hydromorphone and 24 patients (80%)
either refused additional hydromorphone at 15 minutes or received a dose at 15 minutes but
declined a dose at 30 minutes. Dizziness, nausea, headache, and some dissociative effects
were reported.(Ahern 2013) Ketamine administered for analgesia in an urban trauma center was
retrospectively reviewed in 35 patients. The most common chief complaint was abscess (46%).
The median dose of ketamine received was 10 mg (range 5-35 mg); opioids were co-administered
in almost all cases (91%). LDK improved pain scores by at least 3 points in 19/35 patients
(54%). Eight patients did not receive a post-drug administration pain score.(Lester 2010) A
convenience sample of patients was enrolled in an ED based study in British Columbia. Any
patients older than 6 years of age presenting with a painful condition were eligible for
enrollment. Patients had to have a score of at least 50 on a 100-mm visual analog score
(VAS). All patients received 0.5 mg/kg of intranasal (IN) ketamine and could receive a
rescue dose of 0.25 mg/kg IN after 10 minutes for VAS > 50. Within 30 minutes, 35 patients
(88%) had a decrease in VAS of at least 13 mm. Patient reported satisfaction was a mean of 7
(5-9) on a patient satisfaction scale of 1-10. Dizziness, nausea, and fatigue were all
reported.(Andolfatto 2013) IN ketamine was also demonstrated as an effective analgesic in
other pediatric and adult ED based studies.(Yeaman 2013)(Yeaman 2014) While ketamine has
been studied in the ED, the available research has multiple limitations. Most of it consists
of observational or retrospective studies. As such, there could be multiple explanations for
their results due to multiple, uncontrolled confounders. In addition, most studies included
patients with any painful complaint and did not have a comparison or control group. We plan
to conduct a prospective, randomized study of ketamine compared to opioids in long bone
fractures.
emergency department. It is an effective medication that most practitioners are familiar
using. Opioid use is not without risk, however. In managing acute pain, patients may
experience hypotension, respiratory depression, hypoxia, nausea and vomiting, dysphoria, and
itching. Patients at risk for respiratory depression include those with advanced age, renal
failure, or treated with multiple other sedatives.
The current recommended dose for opioid administration for acute pain management is
approximately 0.1 mg/kg as a loading dose, although some sources recommend up to 10 mg for
patients weighing more than 50 kg. (Ducharme 2011; Yak 2011) A single center study
demonstrated that patients received an average of 0.08 mg/kg of morphine, which did not
adequately control their pain; no patient received an initial dose of 10 mg.(Bijur 2012) A
post-operative pain study demonstrated that patients needed on average 12 mg or a mean
weight-based dose of 0.17 mg/kg of morphine to achieve an acceptable level of pain reduction
as determined by a 30 mm change on a visual analog scale.(Aubrun 2003) As such even if
patients received 1 mg of hydromorphone, their pain would still not be adequately
controlled.
Ketamine is a dissociative anesthetic that is a noncompetitive antagonist of
N-methyl-D-aspartate (NMDA) receptors. Low dose ketamine (LDK) (0.03-0.05 mg/kg) has
analgesic properties by modulating opioid tolerance and hyperalgesia.(Uprety 2013)
Currently, ketamine is used in the emergency department for moderate sedations and "awake"
intubations. In the pre-hospital setting, it is used in the management of patients with
excited delirium and pain control.(Keseg 2014)(Wiel 2014)(Jennings 2013) Benefits include
fewer serious adverse effects, especially involving respiratory depression and hypotension
which occurs with high-dose or repeat doses of opioids.(Jennings 2013) In addition to not
causing hypotension, ketamine can elevate a patient's blood pressure, which may be useful in
some circumstances.(Johansson 2009) Emergence delirium is associated with ketamine; this is
a rare adverse event and is usually alleviated with benzodiazepines. Additionally, LDK is
unlikely to cause the emergence delirium or the dissociation usually associated with larger
doses. Another potential complication is laryngospasm. Fortunately, this too is rare and in
most cases, patients are easily bagged through the event.
LDK is efficacious in reducing multiple types of pain in a variety of settings. Ketamine
infusions can reduce pain from vaso-occlusive pain crises seen in patients with sickle cell
anemia.(Uprety 2013)(Neri 2013)(Jennings 2013) In the postoperative setting and intensive
care unit, ketamine reduced the amount of morphine required to control pain.(Galinski
2007)(Bell 2006)(Herring 2013) In out-of-hospital trauma patients, ketamine combined with
morphine produced superior analgesia to morphine alone. All patients received morphine and
were then randomized to receive either morphine or ketamine if further analgesia was
required. Ketamine had a change in the visual analog scale (VAS) of -5.6 (CI -6.2 to -5.0)
while morphine had had a change of -3.2 (CI -3.7 to -2.7).(Jennings 2012) In another
pre-hospital study, ketamine was administered to 1030 patients for pain or anesthesia. No
patients incurred ketamine-induced respiratory adverse events.(Bredmose 2009) Preliminary
studies have also investigated LDK in the emergency department (ED). Available research
mainly consists of retrospective or observational data. In an observational study performed
in an urban ED in California, LDK significantly improved patient's pain without adversely
effecting blood pressure, heart rate, or respiratory drive. Twenty-four patients over age 18
who received ketamine for any reason were included. Three received ketamine for sedation
while the rest received it for analgesia. Most patients received opioids prior to receiving
ketamine, although the opioids did not result in improved pain scores. On a scale of 0 to
10, ketamine reduced pain from 8.9 ± 2.1 to 3.9 ± 3.4 (p<0.0001).(Richards 2013) In another
observational, ED based study, ketamine used as an analgesic was investigated. Thirty
patients with a variety of painful complaints (abdominal pain, back pain, nephrolithiasis,
biliary pain, fractures, sickle cell pain) were enrolled. Patients were initially
administered a combination of hydromorphone 0.5 mg and ketamine 15 mg with rescue doses of
hydromorphone 1 mg available 15 minutes and 30 minutes after the initial dose of analgesia.
In 28 patients (93%), there was a clinically significant decrease of 2 or more points on a
numerical rating score measured after the initial administration; 14 patients reported pain
scores of 0. Fourteen patients refused any additional hydromorphone and 24 patients (80%)
either refused additional hydromorphone at 15 minutes or received a dose at 15 minutes but
declined a dose at 30 minutes. Dizziness, nausea, headache, and some dissociative effects
were reported.(Ahern 2013) Ketamine administered for analgesia in an urban trauma center was
retrospectively reviewed in 35 patients. The most common chief complaint was abscess (46%).
The median dose of ketamine received was 10 mg (range 5-35 mg); opioids were co-administered
in almost all cases (91%). LDK improved pain scores by at least 3 points in 19/35 patients
(54%). Eight patients did not receive a post-drug administration pain score.(Lester 2010) A
convenience sample of patients was enrolled in an ED based study in British Columbia. Any
patients older than 6 years of age presenting with a painful condition were eligible for
enrollment. Patients had to have a score of at least 50 on a 100-mm visual analog score
(VAS). All patients received 0.5 mg/kg of intranasal (IN) ketamine and could receive a
rescue dose of 0.25 mg/kg IN after 10 minutes for VAS > 50. Within 30 minutes, 35 patients
(88%) had a decrease in VAS of at least 13 mm. Patient reported satisfaction was a mean of 7
(5-9) on a patient satisfaction scale of 1-10. Dizziness, nausea, and fatigue were all
reported.(Andolfatto 2013) IN ketamine was also demonstrated as an effective analgesic in
other pediatric and adult ED based studies.(Yeaman 2013)(Yeaman 2014) While ketamine has
been studied in the ED, the available research has multiple limitations. Most of it consists
of observational or retrospective studies. As such, there could be multiple explanations for
their results due to multiple, uncontrolled confounders. In addition, most studies included
patients with any painful complaint and did not have a comparison or control group. We plan
to conduct a prospective, randomized study of ketamine compared to opioids in long bone
fractures.
Inclusion Criteria:
- Eligible Long bone fractures. This will include:
- Humerus
- Tibia
- Fibula
- Femur
- Radius
- Ulna
Exclusion Criteria:
- Injuries older than 24 hours
- Avulsion fractures
- History of substance abuse
- History of chronic opioid dependence
- Pregnancy
- Demonstrates signs of intoxication
- Allergic to ketamine or opioids
- Patients unable to consent
- Hemodynamically unstable (SBP >180mmHg or <100mgHg, HR >130bpm, Respiratory rate <10,
oxygen saturations <90%
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