INTRODUCTION:

Pain is an unpleasant sensory and emotional experience, which is a consequent of real or potential damages to a tissue [1]. Previous studies reported that despite all global efforts such as devising protocols and guidelines, a high percentage of ICU patients still suffer some moderate to severe pains [1]. One of the main reasons of pain in ICU patients is major surgery.

An appropriate pain control will reduce the surgery-induced stress in patients who have undergone a major surgery, and will improve the outcome of the surgical operation [2]. Thus, pharmacologic route is in the first line of treatment of pain in ICU patients [1,3].

Previous studies have reported various results regarding the effectiveness of different methods of administration of analgesic drugs in patients. Sharma et al. studied the effects of epidural injection in thoracic vertebrae during general anesthesia in obese patients under coronary bypass surgery [4].They reported that epidural injection of drugs during general anesthesia improves oxygenation, reduces pain, and reduces length of ICU stay in obese critically ill patients [4]. In another study, Roussier et al. in a randomized double-blind study, studied the effects of patient-controlled cervical epidural fentanyl compared with patient-controlled intravenous fentanyl on the level of pain after pharyngolaryngeal among 42 patients [5].They reported that cervical epidural analgesia may provide marginally better pain relief at rest with no decrease in the fentanyl consumption [5]. Furthermore, Caputo et al. in 2011 conducted a randomized controlled trial study to evaluate the impact of thoracic epidural anesthesia on early clinical outcomes in patients undergoing off-pump coronary artery bypass surgery (CABG) [6]. Results of Caputo et al. study showed that the epidural injection of opioids in patients undergoing cardiovascular surgery can improve the patients’ post-operation oxygenation and reduce their risk of cardiac arrhythmia [6].Moreover, Butcovic et al. in 2007 studied the postoperative analgesia with intravenous fentanyl versus epidural block after thoracoscopic pectus excavatum repair in children [7].They reported that intravenous fentanyl PCA is more effective than thoracic epidural for postoperative analgesia in this group of patients [7].In addition, Butcovic et al. recommended the use of intravenous fentanyl PCA in this group of patients regarding the possible complications of epidural catheterization in children [7].In another study, Murakami et al. compared the intravenous and the epidural injections of fentanyl in terms of their effects on pain severity [8].They reported that the intravenous injection of fentanyl was superior to epidural injection for control of pain [8].In contrast, Block et al. in a meta-analysis of 100 randomized controlled trials which evaluated the use of postoperative epidural analgesia reported that epidural analgesia, regardless of analgesic agent, location of catheter placement, and type and time of pain assessment, which in turn provided better postoperative analgesia compared with intravenous opioids [9].

One of the side-effects of opioids administration for pain alleviation in critically ill patients is the effect of these drugs on the patients’ respiratory function. This side effect is especially more important in patients with thoracic trauma and thoracic surgery. Nevertheless, there is not much information available about this issue. Thus, this study aimed to compare the effects of intravenous and the epidural injections of fentanyl on the patients' level of pain, lungs static compliance, and PaO₂ in ICU patients' with thoracic trauma and surgery.

METHODS:

This study is a randomized controlled trial conducted from September 2011 to January 2012 in three ICUs at the Shahid Bahonar hospital, Kerman, Iran. This hospital has 33 mixed ICU beds which could admit approximately 1104 patients in 2010 [10]. This study has received permissions from deputy of research and also the ethics' board of the Kerman University of Medical Sciences (code: k/89/125). Inclusions criteria of the study were: thoracic trauma, being on mechanical ventilation, having an endotracheal tube, staying in the ICU for at least one day, not be addicted to opium, age between18 to 60 years, and BMI less than 30. Exclusion criteria were spinal injuries, hepatic or renal failure, cardiac ischemia, pneumonia, high blood pressure, diabetes, need to a massive transfusion, shock, adult respiratory distress syndrome, and need to other pain-control medications. Due to low levels of consciousness of patients, all written consents were obtained from patients’ families. According to Privado et al. intravenous fentanyl response rate is 30% and epidural fentanyl response rate is 80% in improvement in pain response (primary outcome in our study) and considering a power of 95% (beta) and P = 0.05% (alpha), the sample size would be 16 in each groups (total 32) [13]. Because our hospital is center of trauma in southeast of Iran, numbers of patients with chest trauma who admitted to our ICU is high. For increasing power of our finding we obtained 60 samples for present study. Eligible patients whom were found at the time of operation room admission, were randomly assigned to group "I" (Intravenous group) or group "E" (Epidural group) by the supervisor of the operation room, who chose the next serially numbered sealed opaque envelope containing a simple 1:1 randomization sequence. In group "E", at the end of surgery, patients were placed in the lateral position and an epidural catheter was inserted in the T11-L1 epidural space (Insertion of epidural catheter for unconscious patients is contraindicated, our patients were alert but due to endotracheal intubation (because of reparatory distress due to thoracic trauma) not able to have verbal response). At the end of insertion, catheters were checked for correct position by administering 3 mL lidocaine 2% with epinephrine 1:200,000. In this group, in the first 24 hours after ICU admission, fentanyl was diluted in 100 cc preservative-free saline and was injected epidurally to the patients with the use of an infusion pump. In group I, in the first 24 hours after admission, fentanyl was diluted in 100 cc preservative-free saline and was injected intravenously to the patients with the use of an infusion pump. The amount of the administered fentanyl was 2 μg/kg/h in the patients of group I (loading dose were 25-100 μg fentanyl intravenously every 5-10 minutes) and 1 μg/kg/h in the patients of group "E".³ We also used similar dose of morphine intravenously in both groups before entering the patients into the study. Moreover, midazolam 0.05 mg/kg was also used every four hours in order to sedate patients in both groups. All medications were available in hospital pharmacy.

Dependent variables were the pain level, pulmonary static compliance, and the PaO₂. They were measured and recorded at 0, 2, 6, and 24 hours after ICU admission. To assess pain intensity, we used the behavior pain scale (BPS) [11]. The patients were assessed every 30 minutes for pain. Lungs static compliance was measured using a ventilator model Bennet 840 (The Puritan Bennett™ 840 ventilator system manufactured in covidien of Ireland) and the relevant formulae. For measuring the PaO₂, one cc blood sample was obtained from each patient arterial line that inserted in radial artery. Then, the blood samples were analyzed using GEM premier 3000 analyzer (Instrumentation laboratory GEM premier 3000 blood gas analyzer of USA). The demographic variables of the patients such as age, gender and weight were found in their files and recorded in the provided forms. Patients' pain was assessed by nurse who trained in pain management in ICU. Other parts of data collection (Lungs static compliance and PaO₂) were performed by intensivist who was not involved in the study. The data analysis was performed using SPSS (Statistical Package for the Social Sciences) version 17. A P value of less than 0.05 was considered as statistically significant. Descriptive statistics (expressed as mean and standard deviation (SD)), ANOVA was used to compare the samples, repeated over time (in each group in times of 0, 2, 6, and 24) and student t test (for comparing the means score of BPS, PaO2 and lung static compliance between two groups (I and E) in every time (0, 2, 6, and 24) were used.

RESULTS:

Of the 60 patients, 46 were men. The mean age of all patients was 37.7±8.3 years. The demographic characteristics including age, race, sex, chest tube insertion (in one or both side of chest), weight, BMI and level of consciousness (GSC) in time of ICU admission were similar in two groups (Table 1). The mean score of BPS showed that patients in both groups experienced a high level of pain at the time of ICU admission. In the first hours after the ICU admission, the pain level was reduced in both groups; however, the patients of Group I had a lower level of pain than the patients of group "E". Two hours after ICU admission, pain was better controlled in patients of group E than patients of group I. (Table 2). The mean of static compliance and PaO₂ in the first 2 hours was higher in the patients of group "I", but after 2 hours, these finding became reversed and the compliance and PaO₂ became higher in the patients of group "E". This difference was statistically significant (P < 0.05) (Tables 3, 4).

Table 1): Charecteristics of the study patients on admission to the ICU

P value	Group E	Group I	Charecteristics
0.09	38.4±6.3	36.9±8.3	Age (years)
_	All Asian	All Asian	Race
0.05	24	22	Male	Sex
0.05	6	8	Female	Sex
0.05	23	21	1 side	Having chest tube
0.05	7	9	2 side	Having chest tube
0.05	8.5±0.6	8.9±0.7	GCS
0.05	73.2±6.3	71.7±8.1	Weight (kg)
0.05	25.2±2.7	24.8±3.1	BMI

Table 2): Mean of BPS in intravenous and epidural group

Mean of BPS			Time (Hour)
P value	Group E	Group I	Time (Hour)
0.07	8.9±0.9	8.6±1.2	0
0.01	6.2±1.5	5.2±0.9	2
0.001	1.7±0.9	4.1±0.9	6
0.009	1.1±0.9	3.4±1.1	24

Table 3): Mean of lungs static compliance in intravenous and epidural group

Mean of Static Compliance			Time (Hour)
P value	Group E	Group I	Time (Hour)
0.09	32.4±7.9	31.9±8.5	0
0.009	34.9±8.5	37.8±9.2	2
0.004	47.6±10.5	40.6±9.2	6
0.006	47.2±8.1	41.2±9.1	24

Table 4): Mean of PaO₂ in intravenous and epidural group

Mean of PaO₂			Time (Hour)
P value	Group E	Group I	Time (Hour)
0.25	87.2±19.2	85.2±23.8	0
0.003	92.1±26.8	89.4±25.3	2
0.001	104.6±28	95.3±27.1	6
0.001	107.6±28.4	96.1±26.2	24

DISCUSSION:

In patients with thoracic trauma whom need mechanical ventilation, a proper analgesia is necessary for proper ventilation. The results of present study showed that the pain controlled more rapidly with intravenous injection of fentanyl in patients with thoracic trauma; however, after a while, when the blood concentration of the fentanyl which was injected in epidural space reaches a maximum, the epidural injection of fentanyl leads to better results.

Della et al. studied the effect of epidural and intravenous injections of opioids on the patients’ level of pain [12]. They reported that the injection of drugs in the epidural space is a suitable route for pain control. They also found that the epidural route is more effective than the intravenous route for pain alleviation [12]. In another study, Privado et al. reported that in term of analgesia, intravenous and epidural injection of opioids are similar, however, they also reported that with the use of epidural method, consumption of analgesic drugs reduced compared to intravenous method [13].Charghi et al. in a retrospective study compared the epidural and the intravenous methods in terms of their effects on pain control in morbidly obese patients undergoing gastric bypass surgery [14], and reported that the intravenous injection of opiate induces a better analgesia than the epidural injection of it [14].The difference between Charghi et al. results and the results of the present study might be due to the potential differences between the participation of patients between these two studies and also the applied method of two studies; since Charghi et al. compared routes of pain control in the obese patients [14]. Control and treatment of pain in this group of patients whom admitted in ICUs is different from other patients [15]. Pain control in critically ill patients is a challenging problem for the health care team. This problem in patients' with thoracic trauma is even more challenging. Moderate-to-severe pain is a potent activator of the “stress response”. Ongoing stimulation of this response can have a detrimental effect on many physiologic functions. Cardiovascular, pulmonary, gastrointestinal, and homeostatic functions may all be negatively affected by poorly controlled pain. An individualized, physician-derived pain management plan is required in order to provide adequate pain management to the thoracic trauma patient [16].

The present study showed that, in the early hours, the lungs static compliance is in a better situation if the fentanyl was injected intravenous rather than epidural; however, in later hours, this effect was reversed. Static compliance describes the change in the volume of lungs as a result of a change in the pressure of the lungs. Thus, pain is a factor which could reduce the lungs static compliance. Apparently, since the intravenous injection of drugs is more rapid-acting than the epidural injection of drugs, those patients whom received their analgesic drug via intravenous injection have a better analgesia compared to those patients whom received their drug via epidural injection. But after a few hours, this effect was reversed in favor of those patients who received their drug via epidural injection. As a result of pain reduction, the respiratory function improved and the lungs compliance also increased. When the pain is alleviated and the lungs compliance is improved, the patient lets the ventilator reached to targeted tidal volume with lower level of pressure. The increase in compliance can reduce atelectasis, so there will be more alveoli involved in ventilation, and gas exchange improved.

Results of our study also showed a better status in PaO₂ in patients whom received epidural injection of fentanyl. In fact, PaO₂ is one of the parameters which could show the status of gas exchange in ICU patients. Gruber et al. studied the effect of epidural injection of bupivacaine on the pulmonary function of patients with chronic obstructive pulmonary disease (COPD) [17]. Similar to our results; they reported that the epidural injection, with an appropriate control of patient’s pain, could improve the pulmonary function as well as increase the patients’ oxygenation status [17]. In a meta-analysis done by Ballantyne et al. the effects of various analgesic modalities on postoperative pulmonary function were examined [18].They concluded that, epidural administration of either opioids or local anesthetics was associated with improvement in pulmonary outcome compared to administration of systemic opioids. They also reported that the use of epidural opioid reduced the risk of atelectasis and pulmonary infection [18]. In another study, Onodera et al. reported that respiratory depression is more frequent using fentanyl intravenously [19].

CONCLUSION:

Patients’ inability to communicate about their pain has made the pain to be a challenging topic in ICU. Pain management is important because increased pain experienced by the critically ill patients can cause physiological and psychological complications [20].Patients with massive thoracic trauma are among the patients who may suffer a lot of pain in ICU. One of the main parts of the service which the medical and care-giving teams offer to the patients with major surgeries is the effort to alleviate pain. Any shortcoming in such a service, contradicts medical ethics. The results of the present study showed that for an ideal pain control, increase in lungs static compliance, and PaO₂ in patients who need mechanical ventilation, one should simultaneously pursue both intravenous and epidural (via a T11-L1 catheter) injection of fentanyl (2 μg/kg/h and 1 μg/kg/h respectively). In addition, this protocol makes it possible for the fast-acting intravenous injection of fentanyl to alleviate the patients’ pain in the first hours; then when the blood concentration of the epidural drug reaches its maximum, the intravenous fentanyl to be discontinued in order to minimize the side effects of systemic opioids (such as sedation and prolongation of mechanical ventilation).

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Received on 25.11.2013 Modified on 15.01.2014

Asian J. Nur. Edu. & Research 4(1): Jan.-March 2014; Page 11-14