Burn injury is among the most severe forms of trauma. Burn pain, in particular, is one of the most severe forms of acute pain experienced by patients (1). It consists of a constant background pain of relatively low intensity on which are superimposed short-lasting peaks of severe to excruciating pain during therapeutic procedures such as dressing changes and physiotherapy (2). Procedure-related pain requires frequent assessment and individual titration for effective pain management (3).
Opioid administration is the mainstay of procedure-related pain management in patients with burns (4). Conventionally, large doses of potent opioids are delivered either by repeated IM or IV injections to alleviate procedure-related pain. Very often the analgesia provided by these regimens is inadequate (2). Patient-controlled analgesia (PCA) allows patients to self-administer small predetermined doses of analgesic medication within limits prescribed by their physician (5), resulting in improved pain relief, avoidance of over- and undermedication, and greater patient satisfaction (2). PCA with a potent, rapid onset and a relatively short-acting opioid such as fentanyl offers a method of providing pain relief during burn dressing changes. The aim of our study was to evaluate the feasibility of using PCA-fentanyl for the management of pain during burn dressing changes and to define the optimal PCA-fentanyl demand dose.
The study protocol was approved by the hospital ethics committee. Written, informed consent was obtained from all eligible patients. This prospective, randomized, double-blinded study was conducted in 60 ASA physical status I and II adults of either sex who had thermal burns of more than 20 percent total body surface area and were scheduled for burn dressing changes. Patients who were confused, who had a history of substance abuse, who had hand injury too severe to allow normal use of the PCA hand-control device, or who had electric burns, compromised airway, or pregnancy were excluded from the study. Other patients excluded were those who required inotropic support or mechanical ventilatory support, those with arterial oxygen saturation (Spo2) of <90 percent on room air, those with significant renal or hepatic insufficiency, and those with a known hypersensitivity to fentanyl.
Patients were assessed for study eligibility before the procedure. Patients considered suitable for the study were instructed in the use of the PCA device and the visual analog scale (VAS) for assessment of pain intensity. They were not aware of the dose and mode of administration of the PCA fentanyl bolus. The burn dressing procedures under PCA-fentanyl were conducted in a dressing area with resuscitative equipment readily available. The patients were fasted overnight. They received no premedication on the day of their dressing procedure.
Each patient received an initial loading dose of IV fentanyl 1 μg/kg 10 min before the procedure. The patients were allocated randomly, in a double-blinded study design, to receive on-demand analgesia with one of the four PCA-fentanyl demand doses—10, 20, 30, and 40 μg. The demand dose was delivered IV at a constant rate by a Perfusor Fm PCA pump (Braun) with a 5-min lockout interval.
The patients were instructed to press the PCA hand-control device during the dressing procedure whenever their pain intensity VAS score was >2. The anesthesiologist performing the assessments was blinded to the demand dose size.
During the dressing procedure, electrocardiogram, heart rate, and SpO2 were monitored continuously. Noninvasive arterial blood pressure, respiratory rate, tidal volume, and peak expiratory flow rate were recorded every 10 min. The number of demands made by the patient and the number of demand doses delivered during the dressing procedure were recorded. The mean number of demands made per 10 min and demand doses delivered per 10 min was calculated, and the demand/delivery ratio was obtained. Pain intensity was assessed by the VAS score. The sedation score was recorded (1 = awake, 2 = mildly sedated, or 3 = cannot be aroused) (2). After the procedure, heart rate, arterial blood pressure, respiratory rate, and SpO2 were recorded every 15 min for 2 h. Nausea, vomiting, or any other adverse effects were noted. At the end of the procedure, the patients were asked whether they were satisfied with the pain relief. Respiratory depression was defined as a respiratory rate of <8 breaths/min. Hypotension was defined as a systolic blood pressure of <100 mm Hg.
Comparison of the mean levels of all variables among groups was made by a one-way analysis of variance. Variation within each group was analyzed by two-way analysis of variance. Differences were considered statistically significant if P < 0.05.
Sixty patients were enrolled in the study; 15 were assigned to each treatment group. There were no statistically significant differences among groups with regard to baseline characteristics or demographics (Table 1).
Baseline VAS scores were comparable in the four groups (VAS ≤2). During the dressing change procedure, mean VAS scores in the fentanyl 10 and 20 μg groups (7.73 ± 1.33 and 7.20 ± 1.21, respectively) were significantly higher than those in the 30 and 40 μg groups (4.47 ± 0.83 and 3.90 ± 0.63, respectively) (all P = 0.000) (Table 2). There were no significant differences in the VAS scores between the 10 and 20 μg groups (P = 0.166) or between the 30 and 40 μg groups (P = 0.260).
The 30- and 40-μg demand dose treatments were superior to the 10- and 20-μg demand dose treatments in reducing both the number of demands made and the number of demands delivered (all P = 0.000). There were no significant differences in the number of demands made between the 10 and 20 μg groups (P = 0.613) or between the 30 and 40 μg groups (P = 0.700). There were no significant differences in the number of demand doses delivered between the 10 and 20 μg groups (P = 0.359) or between the 30 and 40 μg groups (P = 0.511).
The demand/delivery ratios were significantly larger in the 10 and 20 μg groups than in the 30 and 40 μg groups (all P = 0.000). The demand/delivery ratio was comparable between the 30 and 40 μg groups (P = 0.777) (Table 2).
The mean total fentanyl doses delivered in the 10-, 20-, 30-, and 40-μg demand dose groups were 109.33 ± 41.31 μg, 155.00 ± 40.71 μg, 149.01 ± 42.43 μg, and 187.60 ± 49.99 μg, respectively). The mean total fentanyl dose was significantly larger in the 20, 30, and 40 μg groups compared with that in the 10 μg group (all P > 0.05). The mean fentanyl dose received in the 20-μg and 30-μg demand dose groups was comparable (P = 0.610). Patients in the 30 and 40 μg groups were satisfied with the pain relief.
The baseline hemodynamic variables (heart rate and systolic and diastolic blood pressure) and respiratory variables (respiratory rate, tidal volume, peak expiratory flow rate, and SpO2) in the four groups were comparable. There was no significant variation from baseline in these variables during the study period in the four groups.
No patient became sedated. There were no episodes of nausea or vomiting. Dizziness was experienced by 2 patients, one each in the 10 and 30 μg groups, after the administration of the initial fentanyl dose. There were no episodes of hypotension, respiratory depression, or desaturation.
IV PCA has proved to be safe and effective for the management of pain in the burn population (6–8). Kinsella et al. (7) reported on the use of morphine via PCA in 18 nonseriously burned patients after surgery and in 5 acutely burned patients. In the postoperative group, PCA was used for 12 to 24 hours with good results. In the 5 acutely burned patients, morphine at a mean dose of 3.1 mg/h for a mean of 28.3 hours (range, 9.5–72 hours) was also reported to give good results. Choiniere et al. (8) compared IV PCA-morphine to intermittent as-needed IV morphine in 24 adult burn patients in a double-blinded study. Although the amount of morphine was similar between study groups, the group receiving IV PCA-morphine reported better pain relief compared with the control group. The authors suggested, however, that the PCA approach may not suffice for the intense pain levels felt during therapeutic procedures. On these occasions, an IV bolus administered before the procedure may be necessary to supplement the PCA regimen.
Badetti et al. (9) studied fentanyl requirements with PCA during the first six postburn days. They fixed the bolus dose of fentanyl at 1 μg/kg, the lockout interval at 30 minutes, and the 4-hour dose limit at 7 μg/kg. Mean fentanyl delivery was 1.7 ± 0.1 μg · kg−1 · h−1 during dressing periods, 0.9 ± 0.3 μg · kg−1 · h−1 during afternoon periods, and 0.5 ± 0.2 μg · kg−1 · h−1 during overnight periods.
From a pilot study in five patients with thermal burns, Sim et al. (2) suggested that PCA with alfentanil may be an effective form of pain relief for burn dressing procedures. The study by Gallagher et al. (10) supports the efficacy of an operator-adjusted target-controlled infusion of alfentanil to provide analgesia for burn dressing changes.
The efficacy and safety of fentanyl administered by PCA have been extensively evaluated in the management of postoperative pain (11–14). The demand dose of fentanyl in these studies ranged from 10 to 50 μg, and the lockout times between doses ranged from 0 to 15 minutes (15). Optimal efficacy and safety of PCA depends on the selection of a demand dose that is small enough to minimize adverse effects but large enough to achieve analgesic efficacy (15). In this randomized, double-blinded study, we compared 4 demand dose sizes of fentanyl (10, 20, 30, and 40 μg), with lockout intervals of 5 minutes, after an IV initial loading dose (1 μg/kg) for the management of pain of burn dressing changes. The procedure was commenced 10 minutes after the initial dose because although the onset of action of fentanyl is almost immediate when the drug is given IV, the maximal analgesic effect may not be noted for several minutes. There is a distinct time lag between the peak plasma fentanyl concentration and peak slowing on the electroencephalograph. This delay reflects the effect-site equilibration time for fentanyl (6.4 minutes) between blood and brain (16).
Patients receiving a fentanyl demand dose of 30 or 40 μg achieved significantly better pain relief during dressing changes (as evidenced by lower VAS scores) than patients receiving the 10- or 20-μg demand dose.
The numbers of demands made and the demand doses delivered were significantly less in the 30- and 40-μg demand dose groups compared with the 10-and 20-μg demand dose groups. The large demand/delivery ratios in the 10- and 20-μg groups indicate that the patients experienced inadequate pain relief and that their discomfort was great enough to lead them to request additional analgesia. The ratio of demands for analgesia and successful delivery of the drug (demand/delivery ratio) has been used as a guide to the adequacy of analgesia and has been shown to correlate with the VAS (17).
Although the mean total fentanyl doses received in the 20- and 30-μg demand dose groups were comparable (155 and 149 μg, respectively), the VAS scores and demand/delivery ratios were significantly larger in the 20-μg demand dose group than in the 30-μg demand dose group. This could be explained by the difference in demand dose size. The size of demand dose and the duration of the lockout interval limit the dose rate and may be so restrictive that the efficacy of the technique will be suboptimal (18). Therapeutic success with PCA is dependent on the size of the demand dose (19).
The level of analgesia achieved was similar in patients who received 30- and 40-μg demand doses, as indicated by their similar VAS scores and demand/delivery ratios. These findings support the comparable analgesic efficacy of the 30- and 40-μg demand dose size of fentanyl for the management of pain during burn dressings. Because the larger demand dose was not associated with further improvement in analgesic efficacy, we conclude that the optimal demand dose for burn dressing changes in our study was 30 μg.
No hemodynamic changes were observed during the study period, probably because fentanyl provides stable hemodynamics by suppression of the stress response to surgery and because its administration is not associated with histamine release (16). Respiratory depression was not observed. Two patients reported dizziness after the administration of the fentanyl initial loading dose. The patients were conscious, alert, and communicative during the procedure.
Burn pain is extremely variable from one patient to another and undergoes wide fluctuations over time. Because of the wide variability in the pain experienced, pain management needs to be highly individualized. With PCA, the burn patient can titrate his or her medication according to need, and the wide variations in analgesic requirements can be overcome. In conclusion, PCA-fentanyl can be used for the management of pain during burn dressing changes. The optimal PCA-fentanyl demand dose in our study was 30 μg after an IV initial loading dose of 1 μg/kg and a lockout interval of 5 minutes.
We thank Rajvir Singh, PhD, Department of Bio-statistics, All India Institute of Medical Sciences, New Delhi, for statistical analysis.
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