a Departamento de Ortopedia, Santa Casa de São Paulo, São Paulo, SP, Brasil
b Serviço de Ortopedia e Traumatologia, Hospital Israelita Albert Einstein, Universidade Federal de São Paulo (Unifesp), São Paulo, SP,Brasil
c Instituto de Ortopedia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brasil
d Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp), São Paulo, SP, Brasil
Introduction
Despite advances in the treatments for postoperative pain,a large number of patients still suffer after spinal surgery.Most of these surgical procedures cause intense pain duringthe immediate postoperative period, and this may last for atleast three days.1-5This pain may increase morbidity and theincidence of complications, along with delaying rehabilitation.Furthermore, postoperative pain is a risk factor, given that itmay give rise to development of chronic pain syndromes.
Safe and efficient methods for postoperative analgesiaare therefore essential following vertebral arthrodesis proce-dures. Parenterally administered opioids are most frequentlyindicated for analgesia among patients who have undergonelumbar arthrodesis by means of a posterior route.7Epiduralanalgesia has been used in some procedures in the lumbarspine, such as vertebral arthrodesis, laminectomy, discectomy,hemilaminectomy and foraminectomy.8-10However, adminis-tration of opioids intravenously or intramuscularly is generallydone at doses that may cause side effects, such as respiratorydepression, nausea, vomiting, sedation, urine retention, pru-ritus and paralytic ileus.7Other possible causes of pain mayinclude the patient's positioning over the perioperative period;prolonged anesthesia; long posterior surgical incisions, whichgive rise to discomfort in the postoperative position of dorsaldecubitus; large detachment of the paravertebral musculature,which is necessary for surgical access; and long periods of useof surgical retractors.7Since the dural sac is dissected duringthis procedure, morphine can easily and safely be injected intothe epidural region, by the surgeon during the procedure.
This randomized prospective study had the objectives ofcomparing patients who underwent posterior arthrodesis ofthe lumbar spine with untreated patients and ascertaining theefficacy of a single dose of epidural morphine sulfate duringthe immediate postoperative period. ofthe lumbar spinal canal, were operated under general anes-thesia at Hospital Santa Teresa, Petrópolis. Approval for thisstudy was obtained from the institution's ethics committeeand informed consent was obtained from all the patients.Patients were excluded if they presented the following crite-ria: ASA > III, allergy or intolerance to morphine, pregnancy,previous opioid use, preoperative pain other than in the lum-bar spine or previous lumbar spine surgery. After the surgicalprocedure, patients in Group 1 (study group) underwent in situepidural infiltration through the laminectomy area, consistingof 2 mg of morphine sulfate diluted in 10 mL of 0.9% physio-logical serum. Group 2 (controls) did not undergo infiltration.Both groups were evaluated regarding pain levels 24 h beforethe surgical procedure and 18-24 h after the surgery, by meansof a visual analog scale (VAS). This scale formed an instrumentfor measuring the evolution of the pain levels (Table 1).
Statistical methodology
The data observed were analyzed descriptively and presentedin the form of a table showing frequencies (n) and percentages(%) for the categorical data and the mean ± standard deviationand medians for the numerical data.The statistical analysis was composed of the followingmethods:
To ascertain whether there were any significant differencesin the numerical variables between the two groups (studyand control), Student's t test for independent samples orthe Mann-Whitney test was used for nonparametric vari-ables, and the Chi-square test (2) was used for comparingcategorical data (qualitative variables).
To analyze the change in the pain scale from before to afterthe operation, the Wilcoxon signed rank test was used (non-parametric variables).
Nonparametric methods were used because some variables(pain scale and deltas) did not present normal distribution(Gaussian distribution), because of the dispersion of thedata and rejection of the hypothesis of normality accordingto the Kolmogorov-Smirnov test. The criterion adopted fordetermining significance was the 5% level. The statisti-cal analysis was processed by means of the SAS®System
Results
The first objective was to ascertain whether there was any sig-nificant difference in the baseline variables between the twogroups (study and control).
Table 2 presents the frequencies (n) and percentages(%) relating to sex and pathological condition, and themean ± standard deviation relating to age and the corre-sponding descriptive level (p-value) of the statistical test. Thestatistical analysis was composed of the 2test for categoricaldata (sex and pathological condition) and Student's t test forindependent samples (age).
It was observed that there were no significant differencesin the baseline variables between the two groups, at the 5%level.
The second objective was to ascertain whether there wasany significant change on the pain scale from before to afterthe operation. Tables 3 and 4 present the means, standarddeviations (SD) and medians on the pain scale before andafter the operation, the corresponding absolute delta (points)and relative delta (%) and the descriptive level (p value) of theWilcoxon test, separately for the study group (in situ infiltra-tion with morphine sulfate) and control group, respectively.
The absolute delta of the pain scale from before to after thetreatment was given by the formula:
Delta(points) = (preoperative pain - postoperative pain)
It was found that in the study group, there was a significantdecline on the pain scale after the operation, comprising amean of 4.7 points (p = 0.0001), which corresponded to 53.2%(p = 0.0001).
It was found that in the control group, there was a signifi-cant decline on the pain scale after the operation, comprisinga mean of 2.7 points (p = 0.0001), which corresponded to 28.8%(p = 0.0001).
The third objective was to ascertain whether there was anysignificant difference on the pain scale and in the respectivedeltas (absolute and relative) between the study and controlgroups.
Table 5 presents the means, standard deviations (SD) andmedians of the pain scale and the respective deltas (absoluteand relative) according to the group (study or control) and thecorresponding descriptive level (p value) of the Mann-Whitneytest.
It was found that the postoperative declines for the studygroup were significantly greater than those of the controlgroup; such a relative decline was approximately twice asmuch, with regard to the pain scale (p = 0.0001), absolute delta(p = 0.0001) and relative delta (p = 0.0001).
There was no significant difference between the two groupson the pain scale before the operation, at the 5% level(p = 0.086).
Discussion
Perioperative analgesia remains a great challenge for sur-geons, in treating patients through complex spinal surgery.17Since the discovery of opioid receptors in the spinal cordin 1970, many studies have proven the efficacy of epiduralmorphine.18-20Surgery on the posterior region of the spinemay lead to intense postoperative pain because of the exten-sive dissection of soft tissues and the detachment of theparavertebral musculature to obtain adequate exposure of thelamina, facets and transverse processes.
O'Neill et al.8observed that there was a significant reduc-tion in the need for additional analgesic among patients whounderwent lumbar spinal procedures after 1 mg of epiduralmorphine had been administered. However, these authorswarned about side effects. Blacklock et al.12studied fivepatients who underwent lumbar surgery after receiving 1 mgof morphine epidurally, in comparison with a control group.Although the authors observed that there was superior anal-gesia in the study group over the first 24 h, they reportedthat there was a rebound effect with intense pain, such thattreatment with opioids was required between two and fivedays after the operation. The authors concluded that thepain might have been triggered by early movement of thepatient or through reduction in endorphin production. Franceet al.13used a mean epidural morphine dose of 0.91 mg (range:0.4-1.2 mg). The patients had a high level of analgesia over thefirst 24 h after the surgery, with significantly lower use of anal-gesics than what was observed in the placebo group. Theyalso reported that there was a rebound effect after the sec-ond postoperative day. Urban et al.15analyzed the use of twomorphine doses (0.7 and 1.4 mg) in comparison with a controlgroup that did not receive epidural infiltration. Both groupspresented superior analgesia in relation to the control group.These authors concluded that the best results were obtainedamong patients treated with high doses of morphine (1.4 mg).
Techanivate et al.16conducted a placebo-controlled ran-domized prospective study involving 40 patients whounderwent lumbar laminectomy and fusion. They observedthat the group treated with morphine presented significantlylower pain over the first 48 h after the operation, according tothe VAS scoring, than what was observed in the placebo group.
Wu et al.24demonstrated that low morphine doses (1 mg)administered epidurally were sufficient for controlling thepain after decompression surgery and posterior fusion of theshort segment of the spine. These authors observed that lowdoses resulted in fewer side effects than were seen with intra-venous injection of analgesia controlled by the patient, or withinjection of meperidine.
Our study demonstrated that the two groups did notpresent any significant difference (p = 0.086) in relation to pre-operative pain, according to the VAS scoring. This indicatesthat the patients in the two groups had similar intensities ofpain. However, after the study group had been treated with anapplication of 2 mg of morphine sulfate in the peridural region,it was seen after the end of the surgical procedure that the painlevel in this group was significantly lower, according to theVAS scoring. From before to after the operation, the pain leveldecreased by a mean of 4.7 points (p = 0.0001), correspondingto 53.2% (p = 0.0001), in the study. As shown by the results, bothgroups presented significant declines in pain after the treat-ment, but in a differentiated manner, i.e. the group treatedwith morphine sulfate showed a substantial improvement inrelation to the untreated group.
The positive aspect of this study was that it demonstratedthe efficacy of using morphine sulfate, administered in a singledose, to significantly reduce the pain during the immediatepostoperative period. We believe that the negative aspect ofthis study was the lack of follow-up on the evolution of thepain and any side effects that might have occurred.
Conclusion
Application of 2 mg of morphine sulfate in a single dose withepidural infiltration was shown to be a good technique for paintherapy following posterior arthrodesis of the lumbar spine.This resulted in high satisfaction among the patients.
Conflicts of interest
The authors declare no conflicts of interest.
1. Bianconi M, Ferraro L, Ricci R, Zanoli G, Antonelli T, Giulia B,et al. The pharmacokinetics and efficacy of ropivacainecontinuous wound instillation after spine fusion surgery.Anesth Analg. 2004;98(1):166-72.2. Cohen BE, Hartman MB, Wade JT, Miller JS, Gilbert R,Chapman TM. Postoperative pain control after lumbar spinefusion. Patient-controlled analgesia versus continuousepidural analgesia. Spine (Phila PA 1976). 1997;22(16):1892-6.3. Gottschalk A, Freitag M, Tank S, Burmeister MA, Kreil S, KotheR, et al. Quality of postoperative pain using anintraoperatively placed epidural catheter after major lumbarspinal surgery. Anesthesiology. 2004;101(1):175-80.4. Blumenthal S, Min K, Nadig M, Borgeat A. Double epiduralcatheter with ropivacaine versus intravenous morphine: acomparison for postoperative analgesia after scoliosiscorrection surgery. Anesthesiology. 2005;102(1):175-80.5. Lowry KJ, Tobias J, Kittle D, Burd T, Gaines RW. Postoperativepain control using epidural catheters after anterior spinalfusion for adolescent scoliosis. Spine (Phila PA 1976).2001;26(11):1290-3.6. Perkins FM, Kehlet H. Chronic pain as an outcome of surgery.A review of predictive factors. Anesthesiology.2000;93(4):1123-33.7. Raw DA, Beattie JK, Hunter JM. Anaesthesia for spinal surgeryin adults. Br J Anaesth. 2003;91(6):886-904.8. O'Neill P, Knickenberg C, Bogahalanda S, Booth AE. Use ofintrathecal morphine for postoperative pain relief followinglumbar spine surgery. J Neurosurg. 1985;63(3):413-6.9. Blackman RG, Reynolds J, Shively J. Intrathecal morphine:dosage and efficacy in younger patients for control ofpostoperative pain following spinal fusion. Orthopedics.1991;14(5):555-7.10. Ross DA, Drasner K, Weinstein PR, Flaherty JF, Barbaro NM.Use of intrathecally administered morphine in the treatmentof postoperative pain after lumbar spinal surgery: aprospective, double-blind, placebo-controlled study.Neurosurgery. 1991;28(5):700-4.11. Ziegeler S, Fritsch E, Bauer C, Mencke T, Müller BI, Soltesz S,et al. Therapeutic effect of intrathecal morphine afterposterior lumbar interbodyfusion surgery: a prospective,double-blind, randomized study. Spine (Phila PA 1976).2008;33(22):2379-86.12. Blacklock JB, Rea GL, Maxwell RE. Intrathecal morphineduring lumbar spine operation for postoperative pain control.Neurosurgery. 1986;18(3):341-4.13. France JC, Jorgenson SS, Lowe TG, Dwyer AP. The use ofintrathecal morphine for analgesia after posterolaterallumbar fusion: a prospective, double-blind, randomizedstudy. Spine (Phila PA 1976). 1997;22(19):2272-7.14. Boezaart AP, Eksteen JA, Spuy GV, Rossouw P, Knipe M.Intrathecal morphine double-blind evaluation of optimaldosage for analgesia after major lumbar spinal surgery. Spine(Phila PA 1976). 1999;24(11):1131-7.15. Urban MK, Jules-Elysee K, Urquhart B, Cammisa FP,Boachie-Adjei O. Reduction in postoperative pain after spinalfusion with instrumentation using intrathecal morphine.Spine (Phila PA 1976). 2002;27(5):535-7.16. Techanivate A, Kiatgungwanglia P, Yingsakmongkol W. Spinalmorphine for post-operative analgesia after lumbarlaminectomy with fusion. J Med Assoc Thai. 2003;86(3):262-9.17. Gottschalk A, Durieux ME, Nemergut EC. Intraoperativemethadone improves postoperative pain control in patientsundergoing complex spine surgery. Anesth Analg.2011;112(1):218-23.18. Rathmell JP, Lair TR, Nauman B. The role of intrathecal drugsin the treatment of acute pain. Anesth Analg. 2005;101 5Suppl.:S30-43.19. Koulousakis A, Kuchta J, Bayarassou A, Sturm V. Intrathecalopioids for intractable pain syndromes. Acta Neurochir Suppl.2007;97(Pt 1):43-8.20. Greenberg HS, Taren J, Ensminger WD, Doan K. Benefit fromand tolerance to continuous intrathecal infusion of morphinefor intractable cancer pain. J Neurosurg. 1982;57(3):360-4.21. Ray CD, Bagley R. Indwelling epidural morphine for control ofpost-lumbar spinal surgery pain. Neurosurgery.1983;13(4):388-93.22. Greenbarg PE, Brown MD, Pallares VS, Tompkins JS, Mann NH.Epidural anesthesia for lumbar spine surgery. J Spinal Disord.1988;1(2):139-43.23. Johnson RG, Miller M, Murphy M. Intraspinal narcoticanalgesia. A comparison of two methods of postoperativepain relief. Spine (Phila PA 1976). 1989;14(4):363-6.24. Wu MH, Wong CH, Niu CC, Tsai TT, Chen LH, Chen WJ. Acomparison of three types of postoperative pain control afterposterior lumbar spinal surgery. Spine (Phila PA 1976).2011;36(25):2224-31.
