Author:
Ahed Al-Edwan
Samer Alghazawi


Correspondence:
Dr. Ahed Al-Edwan, MD,JBA,
Department of Anaesthesiology, KHMC, Amman, Jordan
Mobile +962-777712553
Email: edwanahed@yahoo.com

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Pain is an extremely complex sensation which is difficult to define and measure in an objective fashion. It has been defined as the sensory appreciation of afferent nociceptive stimulation which elicits an affective (or autonomic) component; both are subjected to rational interpretation by the patient (1).

Postoperative pain is a major cause of ineffective breathing after major lung surgery predisposing patients to hypoxemia. Pain treatment after major surgery is particularly important because the postoperative recovery is dependent on the maintenance of respiratory function.

Postoperative pain differs from other types of pain in that it is usually, but by no means always, transitory with progressive improvement over a relatively short duration of time. Typically, the affective component tends towards an anxiety state associated with diagnosis of the condition and fear of delay in provision of analgesic therapy by attendants (2).

Methods of improving postoperative analgesia include : parenteral and non-parenteral administration of opioids and non steroids, local and regional anesthetic techniques and non pharmacological methods (1). Many of these methods depend on the traditional standard opioid, Morphine. Other agents include Tramadol hydrochloride which is thought to produce analgesia by two distinct actions. Firstly, it has agonist activity at the mu and Kappa opioid receptors. Secondly, it enhances the descending inhibitory systems in the spinal cord by inhibiting noradrenaline reuptake and releasing serotonins from nerve endings (1).

Few investigations have compared the analgesic potency between the standard Morphine and Tramadol equi-analgesic effective doses (3).

The aim of our study was to compare the three postoperative hours of analgesic effectiveness between equi-analgesic doses of Morphine and Tramadol administered intravenously following thoracic surgical procedures.

METHODS
Our prospective double blind study included 100 patients, ASA I-II, of both genders, aged 18-72 years and assigned for different elective thoracic surgical procedures at KHMC during the period from March 2009 to March 2011 after obtaining written informed consent from all patients and local ethics board committee approval. Pregnant patients or patients with any contraindications to the administration of opioids, were excluded.

Under general balanced endotracheal anesthesia with single lumen tube or endobronchial with double lumen tube, the patient was induced using intravenous Propofol 2 mg/kg, cistracurium 0.2mg/kg and Fentanyl 3 mcg/kg with a mixture of gases N2O/O2:70%/30% and Sevoflurane 1-2%. Maintenance of anesthesia was achieved using intravenous cistracurium 0.01 mg/kg with Sevoflurane 1-2% mixed with N2O 70%/O2 30%. The last bolus of intraoperative Fentanyl had to be administered at least 60 minutes before the first bolus of postoperative Morphine or Tramadol was requested according to visual analogue scale. During the surgical procedure, local anesthetics to the surgical wound, the administration of long acting benzodiazepines and non-steroidal anti-inflammatory agents were not allowed. Regional blocks were not permitted in any of the study groups. Non-invasive blood pressure, heart rate, oxygen saturation and end tidal CO2 were monitored throughout the whole procedures.

Postoperatively, patients were randomized into two groups. Group M (n=50) patients received a starting intravenous dose of Morphine 5 mg (Morphine sulphate,10 mg in 1 ml, Martindale, POM, CD) and group T (n=50) patients received a starting dose of Tramadol 100 mg (Tramadol hydrochloride, Mabron 100mg/2ml, MAB/CP 120 AH1) as soon as patients reported pain according to a 4-10 score on VAS. During the first postoperative three hours, another two intravenous doses of 5 mg Morphine and 50 mg Tramadol were administered for analgesia if needed.

At three hours postoperatively, responsives were classified as having no or mild pain or were asleep. Non-responsives are patients having moderate to severe pain.

Pain severity was assessed using a visual analogue scale of 0-10 cm, where : no pain = 0,mild pain = 1-3,moderate pain = 4-7 and severe pain =8-10. The time to onset of adequate analgesia (0-3) was recorded where the first dose was taken as time zero. Sleeping subjects were recorded as responsives assuming that they should not be asleep if they had no or mild pain. A double blind method was used in which the anesthetist and patient were not aware of the investigation.

Statistics
Treatment groups were compared using descriptive statistical methods. Chi-square and Students t test were used. P<0.05 was taken as statistically significant.

RESULTS
Regarding number, age, ASA, weight, gender and procedure, there was no significant differences between the two groups (M,T).


Table 1: Patient study related data

The mean duration time from the last bolus of intraoperative intravenous Fentanyl to the first bolus of Morphine or Tramadol was 85 minutes (P>0.05). The mean time interval between skin closure and the first bolus dose of Morphine or Tramadol was 12 minutes (P>0.05).

At three postoperative hours the responsive incidence was not significant and less in the Tramadol group (70.21%-39) than that of the Morphine group (77.35%-39).

Mean onset of adequate analgesia (no or mild pain) was 21 minutes in the Morphine group and18 minutes in the Tramadol group (P>0.05). The first intravenous dose produced analgesia in 10% of the Morphine patients (5/50) and 14% of the Tramadol subjects (7/50). The second dose achieved proper analgesia during the first three hours in 36% (18) of patients in the Morphine group and 30% (15) of patients in the Tramadol group.

The duration between the initial and second bolus of Morphine was shorter (72 minutes) than of Tramadol (83 minutes). There were no significant differences regarding the interval time between the second (42 minutes) and third bolus (44 minutes) in groups T and M respectively.

Mean total volume of Morphine administered to responsives was 17.2 mg while of Tramadol to respondives was 187.3 mg over the first 180 minutes. Over the first 24 hours, the total volume received by responsives of Tramadol was 340.5 mg and of Morphine was 35.1 mg. Patients requested almost 40-50 % of the 24 hours dose of Morphine and Tramadol respectively, by the end of the first three hours.

Patients in the Tramadol group were asleep (4/36) at three hours evaluation less than in the Morphine group (6/42). The responsive incidence did not differ significantly at the time of procedures.

DISCUSSION
This study has shown that Morphine is equipotent to Tramadol in the first three hours of postoperative analgesia protocol used. There are few pharmacological discrepancies between the two agents. The characteristic of wakefulness with Tramadol is attributed to its non-opioid mode of action. Morphine has increased sedation effect over Tramadol (4).The study demonstrated a non-significant decreased responsive rate in the Tramadol group, more than in the Morphine group.

IASP (International Association for the Study of Pain) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. It is clear from this definition that the degree of tissue damage and perception of pain are not necessarily correlated. Pain perception is a complex phenomenon, involving sensory, emotional and cognitive processes. There is considerable evidence that patients continue to suffer pain, despite a wide range of available analgesic drugs. Effective and repeated assessment of patients is essential in determining optimal analgesic management (5). A recent survey showed that most adults still expect to have significant postoperative pain after surgery. Such concern may be justified because traditional management of postoperative pain using intramuscular or subcutaneous opioid administration was given on demand and often failed to produce good analgesia. Methods of treating postoperative pain are diverse. Of these there is parenteral administration of opioids by : intravenous bolus, continuous intravenous infusion, patient controlled analgesia (by bolus intravenous or bolus and infusion) and subcutaneous. It is possible to improve the quality of analgesia in the postoperative period by giving small incremental doses of opioid intravenously when required. In general, this technique is employed only by anesthetists and experienced nursing staff in the immediate recovery period. The boluses of 50 mg Tramadol and 5 mg Morphine are their respective analgesic efficacy (6). Houmes RJ, et al found that a starting dose of 100 mg of Tramadol attained a therapeutic action in the relief of acute postoperative pain (7). An effect equivalent to a starting bolus of Morphine 10 mg carries high risk of hazards. Therefore, in our study we used a starting 100 mg bolus of Tramadol and 5 mg of Morphine, bearing in mind that consecutive needs for analgesia during the next 2 hours should be equal to the boluses needed for proper analgesia. The analgesia volumes received by responsives in this study recommend an effect ratio of Tramadol to Morphine of 11:1, which is similar to other studies (8). Proper analgesia in the early postoperative period is crucial in controlling the consecutive pain of general and thoracic surgical procedures. Opioids are the most frequently used analgesics for the treatment of postoperative moderate to severe pain (9). Tramadol is a centrally acting analgesic with an opioid and a non-opioid way of action(10). The non-opioid action is delivered via enhancement of descending inhibitory pathways and the two actions are synergistic for analgesia(11). It is potent in moderate to severe postoperative pain using single boluses of 50-100 mg.

The time interval between the starting and second bolus of Morphine was shorter than that of Tramadol and this was attributed to the reduced comparative initial bolus of Morphine 5 mg compared to that of Tramadol 100 mg. Vickers and Paravicini showed a responder frequency of 72.6% and 81.2% in the respective Tramadol and Morphine groups (3).

Our study is limited due to a small study group of population, short time of investigation and lack of other investigated analgesic agents. New agents should be compared with standard drugs. In our study, Morphine was chosen as the comparator because it is the agent most frequently used for early postoperative pain management following surgery.

REFERENCES
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9. Unlugenc H, Vardar MA, Tetiker S. Acomparative study of the analgesic effect of patient controlled morphine, pethidine and tramadol for postoperative pain management after abdominal hysterectomy. Anesth Analg 2008 Jan;106:309-312.
10. Coetzee JF, Loggerenberg HV. Tramadol or morphine administered during operation: Astudy of immediate postoperative effects after abdominal hysterectomy.BJA 1998 Nov;81:737-741.
11. Naguib M,Seraj M,Attia M,et al. Perioperative antinociceptive effects of tramadol .A prospective randomized double blind comparison with morphine. Can J Anesth 1998;45:1168-1175.

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