letter to the editor - Hindawi Publishing Corporationdownloads.hindawi.com/journals/prm/2012/154875.pdf · letter to the editor Pain Res Manage Vol 17 No 5 September/October 2012

353

letter to the editor

Pain Res Manage Vol 17 No 5 September/October 2012

does multimodal analgesia premedication improve the management of carcinoma cervix brachytherapy?

To the Editor:We report a retrospective study of premedication with multimodal analgesia for the management of outpatient carcinoma cervix brachytherapy performed under sedation. High-dose-rate (HDR) brachytherapy is a radiation treatment technique that involves the application of localized internal radiation to the cervix. After the initial external radiation treatment, each patient usually receives three HDR brachytherapy treatments that are administered at weekly intervals. The HDR brachytherapy procedure itself lasts for approximately 2 h and is performed under sedation, with regional or general anesthesia (1-4).

When HDR brachytherapy was initiated at the Ottawa Hospital (Ottawa, Ontario) in July 2008, the first six patients completed their course of treatment under intravenous sedation alone. The seventh patient required a large amount of intravenous sedation and analgesia for the first two treatments; a multimodal analgesia protocol was instituted for the patient’s third treatment and has been continued since. This premedication protocol consisted of two tablets of Tramacet (37.5 mg tramadol and 325 mg acetamino-phen, Janssen-Ortho Inc, Canada) and 75 mg pregabalin, adminis-tered orally on arrival to the brachytherapy unit approximately 2 h before the procedure.

The present retrospective study was undertaken following approval by the Research and Ethics Board of the Ottawa Hospital. The charts of 18 consecutive patients treated at the centre from July 2008 to March 2010 were reviewed. Each patient underwent three HDR brachytherapy treatments. Excluding incomplete or missing records, a total of 39 treatments were analyzed. The study group consisted of 22 HDR brachytherapy treatments that included premedication with orally administered multimodal analgesia. This group was compared with a control group consisting of the preced-ing 17 treatments, which did not include premedication. No sig-nificant difference in demographic variables between the study and control groups was observed. Patients in the study group received a significantly lower mean dose of midazolam (Table 1). Although multimodal premedication also resulted in decreased analgesic requirements, decreased pain scores and a shorter duration of pro-cedure with increased total recovery score and duration of stay, none of these differences were statistically significant. No operative or treatment complications were reported in either group.

We have found that cervical carcinoma is a unique situation in which the patient is often a middle-aged healthy woman with a recent treatment of a genitourinary malignancy with external radi-ation. There is, therefore, an expected increase in anxiety, distress and discomfort in this patient population, especially when pos-itioned in lithotomy for the HDR brachtherapy procedure (5). The procedure itself is associated with pain that is described as mild to moderate in intensity, burning in quality and well localized to the pelvis and perineum (5,6). In this acute pain model, in which neuropathic pain and hyperalgesia may be present, poor response to opioids and benzodiazepines may be expected (3,7). The multi-modal analgesia protocol for HDR brachytherapy used in the present study was designed to address the nature and character of this particular pain model (moderate intensity with hyperalgesia). Pregabalin is not only known to decrease neuropathic pain and hyperalgesia; it also has sedative, anxiolytic and sleep restorative

properties that, in our opinion, make it an ideal premedication for patients undergoing HDR brachytherapy (8,9). Tramadol is a weak opioid agonist with additional analgesic effects through the sero-tonin and norepinephrine reuptake pathways (10). This, in our opinion, gives tramadol a unique effectiveness in treating moder-ately severe acute pain that is associated with hyperalgesia, while maintaining an excellent safety and side-effect profile.

For patients undergoing radiation therapy, remaining pain free and comfortable during the treatment may allow for the procedure to be completed effectively in a short time. No significant changes in sedation, level of consciousness or oxygen saturation that may occur in some patients receiving pregabalin (9) were observed in the study group. The increased duration of stay may suggest a pro-longed recovery period in the study group administered premedica-tion, although the study was not powered to demonstrate this difference. Nevertheless, the present retrospective quality assur-ance study contributes to our experience of safety with 'out of operating room sedation' reflected in the smaller dose ranges of intravenously administered drugs during the procedure. We hypoth-esize that this may be due, in part, as previously explained, to a 'normalization' of the hyperalgesia in some of the patients under-going radiation therapy (9).

The drawbacks of the present retrospective study include the small sample size, its retrospective design, and lack of blinding or control for other variables. While the present study suggests that premedication with multimodal analgesia may improve the man-agement of HDR brachytherapy, further research is required in this area.

Naveen Eipe MDJohn Penning FRCPC

Rya Boscariol MDDepartment of Anesthesiology;

Rajiv Samant FRCPCChoan E FRCPC

Department of Radiation Oncology, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario

Continued on page 354

©2012 Pulsus Group Inc. All rights reserved

Table 1Outcomes in study variables in control and study groups

Study variable

Control group (n=17)

Study group (n=22)

estimate of difference P

Midazolam, mg 3.4±2.8 2.8±0.9 –1.49±0.73 0.0485Morphine equivalents, mg

11.9±4.5 9.9±3.4 –4.65±3.96 0.2513

Pain, 0 to 2 1.8±0.2 1.7±0.2 –0.008±0.10 0.9392Duration of procedure, min

153.6±36.2 147.9±43.1 –11.47±19.37 0.5615

Duration of stay, min 202.4±76.7 242.2±62 27.74±33.93 0.4255Total recovery score, 0 to 12

11.7±0.3 11.6±0.4 0.015±0.15 0.9193

Data presented as mean ± SD unless otherwise indicated. Differences between groups were estimated by mixed-model analysis for each vari-able, demonstrating the impact of pre-emptive treatment.

Correspondence: Dr Naveen Eipe, The Ottawa Hospital, University of Ottawa, 1053 Carling Avenue Suite B310, Ottawa, Ontario K1Y 4E9. Telephone 613-761-4169, fax 613-761-5209, e-mail [email protected]

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REFERENCES1. Lim KH, Lu JJ, Wynne CJ, et al. A study of complications arising

from different methods of anesthesia used in high-dose-rate brachytherapy for cervical cancer. Am J Clin Oncol 2004;27:449-51.

2. Kathirvel S, Sadhasivam S, Saxena A, Kannan TR, Ganjoo P. Effects of intrathecal ketamine added to bupivacaine for spinal anaesthesia. Anaesthesia 2000;55:899-904.

3. Benrath J, Kozek-Langenecker S, Hüpfl M, Lierz P, Gustorff B. Anaesthesia for brachytherapy – 5 1/2 yr of experience in 1622 procedures. Br J Anaesth 2006;96:195-200.

4. Roessler B, Six LM, Gustorff B. Anaesthesia for brachytherapy. Curr Opin Anaesthesiol 2008;21:514-8.

5. Velji K, Fitch M. The experience of women receiving brachytherapy for gynecologic cancer. Oncol Nurs Forum 2001;28:743-51.

6. Rollison B, Strang P. Pain, nausea and anxiety during intra-uterine brachytherapy of cervical carcinomas. Support Care Cancer 1995;3:205-7.

7. Altis K, Schmidtko A, Angioni C, et al. Analgesic efficacy of tramadol, pregabalin and ibuprofen in menthol-evoked cold hyperalgesia. Pain 2009;147:116-21.

8. O'Connor AB, Dworkin RH. Treatment of neuropathic pain: An overview of recent guidelines. Am J Med 2009;122:S22-32.

9. Eipe N, Penning J. Postoperative respiratory depression with pregabalin: A case series and decision algorithm. Pain Res Manage 2011;16:353-6.

10. Desmeules JA, Piguet V, Collart L, Dayer P. Contribution of monoaminergic modulation to the analgesic effect of tramadol. Br J Clin Pharmacol 1996;41:7-12.

Poster Presentation: Canadian Anesthesiologists Society, Toronto (June 2011) and International Anesthesia Research Society, Boston

(May 2012).The authors have no conflicts of interest or financial disclosures to declare.

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letter to the editor - Hindawi Publishing Corporationdownloads.hindawi.com/journals/prm/2012/154875.pdf · letter to the editor Pain Res Manage Vol 17 No 5 September/October 2012