BACKGROUND
Although pain is a well-recognized component of appropriate
burn management, the available data suggests that burn pain is undertreated and
is one of the most difficult types of pain to manage. In the short term,
uncontrolled pain is associated with an increased risk of wound infection,
longer hospitalization, poor compliance with rehabilitation therapy, and
increased psychological stress. Acute uncontrolled pain also increases the risk
of depression, PTSD, and attempted suicide after hospital discharge. Up to 52%
of patients with uncontrolled acute pain develop chronic pain syndromes which
can persist for up to 11 years post injury.
The pathophysiology of burn pain is complex and involves
multiple neurotransmitters, meaning appropriate management must be comprehensive
and multi-modal. Appropriate pain management is further complicated by
development of opioid-induced hyperalgesia (OIH) and NMDA-mediated central
sensitization which, if unaddressed, may lead to chronic pain syndromes.
Additionally, acute decreases in renal and hepatic perfusion during the first
48 hours after burn injury may decrease drug clearance; after the first 48
hours, hypermetabolism likely increases drug clearance, and changes in plasma
protein concentrations may increase the unbound drug fraction leading to
hyperresponsiveness to various medications.
Burn pain is generally divided into three subtypes. Background pain is a consistent, dull
pain that is related to tissue injury and may be complicated by anxiety related
to patient illness and immobility. Procedural
pain is high-intensity, short-lasting pain associated with wound cleaning,
dressing changes, debridements, line insertions, and PT/OT. Breakthrough pain is an unpredictable
surge in pain that may happen at any time throughout the day. Intense tingling
and itching as well as neuropathic pain may also occur as tissue regenerates.
PHARMACOLOGY
For typical
dosing and titration parameters, see Tables 1 and 2 and Figure 1. The
information below is intended to help guide selection of adjunctive medications
using patient information.
Acetaminophen (APAP) is a mild analgesic that
becomes more effective when added to baseline opioids. For small burns,
monotherapy with APAP may provide adequate analgesia. In more severe burns, the
addition of APAP to baseline opioids has been shown to be as effective as
higher doses of opioids. Unless there are known contraindications such as
cirrhosis, all patients with burn pain should receive APAP.
Alpha-2 Agonists such as clonidine and
dexmedetomidine work through central modulation of pain perception and
inhibition of substance P. Adjunctive clonidine has been shown to decrease
opioid requirements, improves analgesia, and prolongs anesthetic action.
Dexmedetomidine is generally a more effective sedative and analgesic than
clonidine owing to its increased specificity for the A2 subtype of the alpha-2
receptor. Single-dose dexmedetomidine, when added to opioids and ketamine, has
been shown to improve procedural analgesia. In the acute phase of burn (1st
48 hours), cardiac depression with dexmedetomidine may preclude use in unstable
patients, however when administered with ketamine the drug appears to have
minimal cardiac depressive effects.
Benzodiazepines have no
analgesic properties, but may improve associated anxiety and distress in
patients with severe burns. The addition of low-dose benzodiazepines to both
opioids and ketamine has been shown to improve procedural pain, and
intermittent administration of low-dose lorazepam has been shown to improve
opioid responsiveness in patients with severe breakthrough pain. In patients
with mild pain, benzodiazepines are unlikely to be of benefit and should
generally not be used given their side effect profile.
Gabapentinoids such as gabapentin and pregabalin
work through inhibition of voltage-gated calcium channels to decrease release
of excitatory neurotransmitters and increase inhibitory GABA release. Available
data has shown an inconsistent opioid-sparing effect of gabapentin in the
management of burn pain, however the drug has been successfully used to manage
itching and neuropathic pain. Further, multimodal analgesia likely decreases
the incidence of OIH, therefore gabapentin adjunctive therapy is recommended for
patients with severe burns. Pregabalin is similar to gabapentin, however as it
is a newer drug use is generally limited to neuropathic pain.
NMDA Antagonists such as ketamine and methadone have
gained popularity as adjunctive therapy for the management of severe burns. As
NMDA is postulated to be involved in the development of OIH, addition of
antagonists at this receptor may improve responsiveness to opioids. A
restrospective study of 70 patients with severe burns showed early initiation
of methadone therapy (within 4 days of admission) was associated with increased
ventilator-free days as compared to standard opioid monotherapy. Additionally,
published protocols suggest methadone can be effectively used to decrease
opioid requirements in patients receiving high-dose opioid therapy. Ketamine
has been used both for procedural and background pain, but the majority of data
supports use in the procedural setting. Generally, intravenous doses of
0.6-1.3mg/kg are required for an anesthetic response (absence of nociception).
Ketamine is associated with an emergence phenomenon as well as an increase in
cardiac activity. Co-administration with benzodiazepines may ameliorate the
emergence phenomenon, and dexmedetomidine may improve both emergence and
cardiac response.
NSAIDs such as ibuprofen are quite useful
adjunctive therapies in minor (<15-20% TBSA) burns as they are opioid
sparing and may alleviate OIH. However, routine use is not recommended in
severe burns given the increased risk of renal failure, platelet dysfunction,
and gastrointestinal ulceration/irritation.
Opioids such as morphine, fentanyl,
oxycodone, and hydromorphone generally constitute the backbone of successful
pain management, especially for large (>20% TBSA burns). Although their use
is complicated by adverse reactions including constipation, respiratory
depression, dependence, and possibly immunosuppression, opioids are
advantageous in that they have no ceiling effect for analgesia. Of importance
is the development of OIH and tolerance, both of which may decrease
effectiveness of opioids. To minimize development of OIH, daily sedation
holidays are strongly encouraged for patients receiving continuous infusion
opioids. Further, mixed opioid analgesia (e.g., scheduled oral morphine with as
needed oral oxycodone) may decrease the incidence of OIH, as will including the
adjunctive therapies mentioned. In patients who develop OIH, decreasing the
dose of opioid may improve analgesia. Alternatively, changing to an alternative
opioid at a lower dose may prove efficacious, as will adding an NMDA antagonist
(e.g., methadone) while decreasing the opioid dose. It is likely that semi- or
fully synthetic opioids may induce less histamine release than morphine, which
is of importance in patients who complain of itching.
Miscellaneous
therapies such as synthetic cannabinoids and anesthetics may be
of benefit as well. Although reports of successful use are limited, addition of
dronabinol may moderately improve analgesia in patients with a history of THC
use. Systemic lidocaine may also be of benefit, however use is limited at this
time. Transdermal lidocaine should not be used as changes in absorption when
applied to non-intact skin may cause life-threatening toxicity.
Nonpharmacologic
therapies such
as hypnosis, avoidance techniques, and preparatory/behavioral interventions may
also be useful adjuncts to therapy and may be considered in appropriate
patients. When combined with pharmacologic analgesia, hypnosis has been shown
to reduce grafting needs and decrease hospital length of stay.
NOTABLE REFERENCES
1. Faucher L, Furukawa K. Practice
guidelines for the management of pain. J
Burn Care Res 2006; 27: 659-68.
2. Fry C, Edelman LS, Cochran A.
Response to a nursing-driven protocol for sedation and analgesia in a burn-trauma
ICU. J Burn Care Res 2009; 30: 112-8.
3. Jones GM, Porter K, Coffey R, et al.
Impact of early methadone initiation in critically injured burn patients: a
pilot study. J Burn Care Res 2013;
34: 342-8.
4. MacPherson R, Woods D, Pengold J.
Ketamine and midazolam delivered by patient-controlled analgesia in relieving
pain associated with burns dressings. Clin
J Pain 2008; 24: 568-71.
5. Richardson P, Mustard L. The
management of pain in the burns unit. Burns
2009; 35: 921-36.
6. *Retrouvey H, Shahrokhi S. Pain and
the thermally injured patient – a review of current therapies. J Burn Care Res 2015; 36: 315-23.
7. Zor F, Ozturk S, Bilgin F, et al.
Pain relief during dressing changes of major adult burns: ideal analgesic
combination with ketamine. Burns
2010; 36: 501-5.
*of particular
interest
Table 1. Suggested Oral Background/Breakthrough Pain
Regimens
|
|||||
Regimen
|
Drugs Involved
|
Starting Dose
|
Titration
|
Maximum Dose
|
|
Large Burn
(>15-20% TBSA), Prior fentanyl requirement ≤50mcg/hr |
Morphine IR1
|
15mg q4h
|
15mg per dose, titrate daily
|
N/A2
|
|
Oxycodone/APAP
|
5/325mg, 1-2 tabs q4h PRN
|
N/A
|
2 tabs q4h
|
||
Gabapentin
|
300mg TID
|
100mg per dose, titrate daily
|
2400mg per day
|
||
Clonidine
|
0.1mg BID
|
0.1mg per dose, titrate daily
|
0.5mg q6h
|
||
Lorazepam3
|
1mg q4h PRN
|
N/A
|
1mg q4h PRN
|
||
Large Burn
(>15-20% TBSA), Prior fentanyl requirement >50mcg/hr |
Morphine IR1
|
30mg q4h
|
15mg per dose, titrate daily
|
N/A2
|
|
Oxycodone/APAP
|
5/325mg, 1-2 tabs q4h PRN
|
N/A
|
2 tabs q4h
|
||
Gabapentin
|
300mg TID
|
100mg per dose, titrate daily
|
2400mg per day
|
||
Clonidine
|
0.1mg BID
|
0.1mg per dose, titrate daily
|
0.5mg q6h
|
||
Lorazepam3
|
1mg q4h PRN
|
N/A
|
1mg q4h PRN
|
||
Small Burn
(<15-20% TBSA)
|
APAP
|
975mg q6h
|
N/A
|
975mg q6h
|
|
Ibuprofen
|
400mg q6h
|
200mg per dose
|
800mg q6h
|
||
Oxycodone
|
5mg q4h PRN
|
5mg per dose
|
N/A
|
||
Note: attempt to wean pain medications daily as
appropriate.
1For patients with documented morphine allergy,
consider hydromorphone 2-4mg PO q4h starting dose.
2For doses > 60mg q4h, consider addition of
methadone 5mg PO TID with concomitant 50% reduction in morphine dose.
3Only
consider for high pain scores
Table 2. Potential Procedural Pain Regimens
|
|||||
Regimen
|
Drugs Involved
|
Starting Dose
|
Timing of First Dose
|
Repeat Dosing
|
Maximum Dose
|
Large Procedure, 1st 48 hours
|
Ketamine
|
1mg/kg IV
|
Beginning of procedure
|
0.5-1mg/kg IV q15min PRN
|
4mg/kg
|
Midazolam
|
0.05mg/kg IV
|
Beginning of procedure
|
N/A
|
N/A
|
|
Tramadol
|
1.5mg/kg PO
|
30min before procedure
|
N/A
|
N/A
|
|
Fentanyl
|
N/A
|
N/A
|
50-100mcg IV q15min PRN
|
N/A
|
|
Large Procedure, After 1st 48 hours
|
Ketamine
|
1mg/kg IV
|
Beginning of procedure
|
0.5-1mg/kg IV q15min PRN
|
4mg/kg
|
Dexmedetomidine1
|
1mcg/kg IV
|
Beginning of procedure
|
N/A
|
N/A
|
|
Tramadol
|
1.5mg/kg PO
|
30min before procedure
|
N/A
|
N/A
|
|
Fentanyl
|
N/A
|
N/A
|
50-100mcg IV q15min PRN
|
N/A
|
|
Large Procedure, After 1st 48 hours
(alternate)
|
Ketamine 10mg/mL + Midazolam 0.5mg/mL
IV PCA (20mL)
|
1mL bolus with 3min lockout, no basal
rate
|
|||
Small Procedure
|
Tramadol
|
1.5mg/kg PO
|
30min before procedure
|
N/A
|
N/A
|
Lorazepam
|
1-2mg PO
|
30min before procedure
|
N/A
|
N/A
|
|
Morphine2
|
N/A
|
N/A
|
2-4mg IV q30min
|
N/A
|
|
Small Procedure (alternate)
|
Morphine2
|
2-4mg IV
|
Beginning of procedure
|
2-4mg IV q30min
|
N/A
|
Lorazepam
|
1-2mg IV
|
Beginning of procedure
|
N/A
|
N/A
|
|
Note: continue background pain medications throughout
procedure.
1Give slow IV push over 5-10 minutes.
May consider continuous IV infusion of 0.5-1mcg/kg/hour for duration of
procedure at attending discretion.
2In patients with documented morphine
allergy, consider hydromorphone 0.3-0.6mg IV starting dose, followed by
0.3-0.6mg IV q30min PRN
