Scientific and Technologycal Research

 

Pain and Sensory Symptoms Following Augmentation Mammoplasty: A Long Term Follow-Up Study with Intraoperative Ketamine Use

 

Luis Enrique Chaparro*, Yamile Muñoz Pérez**, Carlos Alberto Gallo***, Hugo Alexánder Álvarez**, Sandra Milena Restrepo Restrepo****, Natalia Pérez*****, Lina Restrepo******

* Profesor asociado de Anestesia y Medicina del Dolor, Universidad Pontificia Bolivariana. Medellín, Colombia. luisdr74@yahoo.com

** Anestesiología, Universidad de Antioquia. Medellín, Colombia.

*** Especialista en Dolor y Cuidados Paliativos, Universidad Pontificia Bolivariana. Medellín, Colombia.

**** Residente de Anestesiología, Universidad Pontificia Bolivariana. Medellín, Colombia.

***** Medicina General, Universidad de Antioquia. Medellín, Colombia.

****** Residente de Medicina Interna, Universidad de Antioquia. Medellín, Colombia.

Recibido: enero 13 de 2010. Enviado para modificaciones: febrero 15 de 2010. Aceptado: marzo 15 de 2010.

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ABSTRACT

Introduction. Augmentation mammoplasty is a common procedure but pain sequelae and sensory symptoms are unknown.

Objective. To assess the impact of using perioperative Ketamine for painful sequelae and neurological symptoms in patients undergoing augmentation mammoplasty.

Methodology. Long-term follow-up of a clinical study including 106 patients that underwent cosmetic augmentation mammoplasty to assess the effectiveness of Ketamine for postoperative pain. Pain intensity and the presence/absence of neurological symptoms were recorded.

Results. A total of 50 patients agreed to participate by responding to a telephone interview. The groups did not differ in terms of demographic variables and the surgical technique. Both groups reported a high incidence of moderate/severe pain on the first day and the week following the operation (19 and 21 patients in the Ketamine and placebo groups, respectively), with complete resolution of symptoms after three months. Three participants in the Ketamine group reported persistent hypoesthesia and one reported a burning sensation. These symptoms were slightly more frequent in the placebo group, with 7 patients reporting hypoesthesia and two burning sensation.

Conclusions. In this study, Ketamine had no significant incidence on chronic pain following cosmetic augmentation mammoplasty. There is a trend suggesting that Ketamine could play a role in reducing the neurological symptoms that exceeded the expected frequency (20 %).

Key words: Follow-up studies. Ketamine, therapeutic use, mammoplasty, adverse effects, postoperative pain (Source: MeSH, NLM)

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INTRODUCTION AND OBJECTIVES

Cosmetic surgery and augmentation mammoplasty in particular, has experienced a considerable growth in Colombia in the last few years. Unfortunately, the incidence of persistent pain and neurological symptoms is unknown. Recent publications seem to disagree with regards to the incidence of this events (1,2).

There are divided opinions with regards to the etiology of the problem. Some believe it is due to persistent inflammation, nerve fiber injury or even a combination thereof (3). Factors such as the presence of intense acute postoperative pain, the use of multimodal perioperative analgesia, the surgical technique and even psychosocial factors, i.e. pre-surgical anxiety, may be determining factors in the development of the condition (4).

A paper previously published by our group showed that the use of Ketamine as an infusion tended to reduce both the intensity of pain and the use of post-surgical meperidine, as well as a non-significant trend to reduce the incidence of post-surgical vomiting in patients who under went cosmetic augmentation mammoplasty (5). The intent of this follow-up study extending beyond one year was to assess whether Ketamine could –on account of its antihyperalesic properties (6,7)– have any influence on the persistence of pain and sensory symptoms in this cohort of patients.

MATERIALS AND METHODS

A cohort, retrospective, follow-up study of a randomized clinical trial (5) that was approved by the Ethics Committee of the out-patient surgical care university clinic (IPS Universitaria) and by the Education Committee of the Department of Anesthesia of the Antioquia University. The follow-up process was by telephone interview or by e-mail; the patients participating in the clinical trial were asked to make up to five contacts. After explaining the purpose of the trial and upon the acceptance to participate in the follow-up, the patients completed a questionnaire that included population variables, change in the size of their bra, surgical technique and any post-surgical adverse events. The participants were identified by code during the final process of analysis of the information and the interviewers didn’t know if the patient received Ketamine or placebo during the initial clinical trial.

The outcome variables included memories of pain severity in the recovery room and at various time intervals (selected arbitrarily by the authors) from the moment they returned home and up to the first week after surgery (subacute phase) and then from three months and up to the time of the survey (chronic phase). In order to preserve the clinical significance –considering that this was a retrospective report– the pain intensity was not assessed with a numerical scale as is usually the case, but with a categorical scale (no pain, mild, moderate or severe pain). Finally, a report of moderate or intense pain was considered clinically significant. The secondary variables included questions about the development of symptoms such as neuropathic pain (stabbing pain, burning sensation, hypoesthesia and dysesthesia) during the same periods of time. To avoid any biases in the information, female health professionals administered the survey.

STATISTICAL ANALYSIS

An Excel (Microsoft Corp. Microsoft Office Version 97-2000) database was developed. The demographic analysis used mean or average measurements, in accordance with the distribution of variables and measures of dispersion such as the standard deviation. To assess the relationship among qualitative variables, the chi-square test was used, including McNemar’s test and the Student’s-T test for the quantitative variables. The logistical regression test was administered in those cases where a multivariate analysis was used, considering factors such as the type of incision, type of follow-up, age and placement of the implant. The statistical package used was Cytel Studio 8.0 (Cytel Corp. Massachusetts, USA). The cut point for statistical significance was p < 0,05.

RESULTS

Of the initial study group, information was obtained from 25 patients that received Ketamine and 25 patients receiving placebo (figure 1). The demographic variables were similar (table 1). The average follow-up was 18.9 months (SD = 1.96) and 19.03 months (SD = 1.98) respectively.

With regards to the memories of acute postoperative pain (table 2), the participants reported a high incidence of pain and neuropathic symptoms. There was a lower incidence of these symptoms (burning sensation and hypoesthesia) among the group of patients that received Ketamine, although the difference was not statistically significant.

No differences were found during the sub-acute phase. There were no reports of moderate or severe pain during the chronic phase; however, three patients, two from the placebo group and one from the Ketamine group, had persistent burning sensation. Hypoesthesia persisted in three patients (12 %) in the Ketamine group versus seven (28 %) patients in the control group (p = 0.17; RR 0.43 [IC 95 %: 0.12 - 1.47]).

DISCUSSION

The role of Ketamine in reducing the incidence of chronic pain is unknown due to a lack of randomized, long-term follow-up studies (8), although there are some on-going prospective studies supporting the clinical significance of our work (clinicaltrials.gov Identifier: NCT00618423). It was shown that Ketamine has a protective effect by reducing the painful and neuropathic symptoms during the postoperative period but did not reach statistical significance mainly because of the small sample size. Though we observed a significant incidence of neurological symptoms, such as pain, burning sensation and hypoesthesia those usually resolved during the first post-surgical week; however, there was a 20 % persistence of hypoesthesia of the surgical area and 6 % persistence of burning sensation out of the total number of cases. Each clinician shall then individually interpret these findings.

It is important to stress that the literature in plastic surgery journals, reports incidences of hypoesthesia from 4 % to 11% (1), but recent studies on the same surgical model report incidences of sensory abnormalities between 30 % and 56 % of the cases (2). The same study reports an incidence of evoked pain of around 13 % in one year of follow-up.

Our interest in doing the follow-up was based on the neuro-physiological presumption that in the case of acute severe pain –as was the case in the original trial– there had to be a higher probability of postoperative pain persistence (9), even more so in a very innervated area such as the breast. Furthermore, we were curious about the incidence of the event in a procedure that is so strongly encouraged in our environment. The incidence of chronic postoperative pain tends to be related to the persistence of neuropathic symptoms such as burning sensation and hypoesthesia; surprisingly enough, our patients denied the persistence of pain, but this could be due to the selection bias that urged the patients who were more pleased with the results to be more willing to cooperate with the survey and to psychosocial factors related to the procedure (10).

A lot has been said about the role of the surgical technique as a predisposing factor for the development of chronic pain in other surgical models like the inguinal herniorrhaphy, where the incidence of chronic pain is around 10 % (11). In augmentation mammoplasty, the retromuscular approach enhances the possibility of nerve bundle manipulation, increasing the probability of inducing persistent postoperative pain (2,12). The periareolar incision seems to promote the development of severe pain (13). It should be emphasized that in the original clinical study, the plastic surgeon did not administer any local anesthetic infiltrations, and in most of our patients, the technique used was the retromuscular approach; hence it is impossible to determine the importance of these factors in our study. The only intervention that has proven to show long term incidence of sensory changes (hypoesthesia and hyperesthesia), with no relevant incidence of pain following augmentation mammoplasty is the use of 125 mg of methylprednisolone (2). The systematic use of 4 mg dexametasone for the prevention of post-surgical nausea and vomiting has been standardized at our institution, though a dose increase to 8 mg has been recently suggested for added analgesia (14-16).

Follow-up studies pose a myriad of obstacles. In our study, most patients came from abroad to undergo their surgeries; other important factors were change of domicile, wrong telephone numbers and the fact that patients wanted to preserve their intimacy.

In conclusion, sensory disorders following augmentation mammoplasty are a real and significant concern that mostly tends to resolve between the first week and the first three months after surgery. However, persistent hypoesthesia is a fact and it should be discussed with patients who want to undergo surgery. Additional studies are required to determine the protective role of Ketamine.

ACKNOWLEDGEMENTS

We want to express our gratitude to the participants in the study for their generous contribution in sharing their experience; to the outpatient surgical unit of the University of Antioquia, and to Dr. Flavio Bohórquez, plastic surgeon and dear friend. Finally, we would like to thank Dr. Fernando Montoya for his generous support with the statistical analysis.

REFERENCES

1. Stoff-Khalili MA, Scholze R, Morgan WR, Metcalf JD. Subfascial periareolar augmentation mammaplasty. Plast Reconstr Surg. 2004;114(5):1280-8; discussion 1289-91.

2. Romundstad L, Breivik H, Roald H, Skolleborg K, Romundstad PR, Stubhaug A. Chronic pain and sensory changes after augmentation mammoplasty: long term effects of preincisional administration of methylprednisolone. Pain. 2006;124(1-2):92-9.

3. Wilder-Smith OH, Arendt-Nielsen L. Postoperative hyperalgesia: its clinical importance and relevance. Anesthesiology. 2006;104(3):601-7.

4. Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth. 2008;101(1):77-86.

5. Chaparro LE, Giraldo N, Pabón LF, Agudelo S, Castillo JM, Gómez I. Efectividad de la ketamina para reducir los requerimientos perioperatorios de opioides. Rev Col Anest. 2005;33(3):169-74.

6. De Kock MF, Lavand'homme PM. The clinical role of NMDA receptor antagonists for the treatment of postoperative pain. Best Pract Res Clin Anaesthesiol. 2007;21(1):85-98.

7. Woolf CJ. Central sensitization: uncovering the relation between pain and plasticity. Anesthesiology. 2007;106(4):864-7.

8. Bell RF, Dahl JB, Moore RA, Kalso E. Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev. 2006(1):CD004603.

9. Poleshuck EL, Katz J, Andrus CH, Hogan LA, Jung BF, Kulick DI, et al. Risk factors for chronic pain following breast cancer surgery: a prospective study. J Pain. 2006;7(9):626-34.

10. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006;367(9522):1618-25.

11. Nienhuijs S, Staal E, Strobbe L, Rosman C, Groenewoud H, Bleichrodt R. Chronic pain after mesh repair of inguinal hernia: a systematic review. Am J Surg. 2007;194(3):394-400.

12. Tebbetts JB. Achieving a predictable 24-hour return to normal activities after breast augmentation: part I. Refining practices by using motion and time study principles. Plast Reconstr Surg. 2002;109(1):273-90; discussion 91-2.

13. Gryskiewicz JM. Avoiding pain and suffering after breast augmentation. Plast Reconstr Surg. 2002;110(7):1812-3.

14. Fukami Y, Terasaki M, Okamoto Y, Sakaguchi K, Murata T, Ohkubo M, et al. Efficacy of preoperative dexamethasone in patients with laparoscopic cholecystectomy: a prospective randomized double-blind study. J Hepatobiliary Pancreat Surg. 2009;16(3):367-71.

15. Jokela RM, Ahonen JV, Tallgren MK, Marjakangas PC, Korttila KT. The effective analgesic dose of dexamethasone after laparoscopic hysterectomy. Anesth Analg. 2009;109(2):607-15.

16. Koc S, Memis D, Sut N. The preoperative use of gabapentin, dexamethasone, and their combination in varicocele surgery: a randomized controlled trial. Anesth Analg. 2007;105(4):1137-42, table of contents.

1. Stoff-Khalili MA, Scholze R, Morgan WR, Metcalf JD. Subfascial periareolar augmentation mammaplasty. Plast Reconstr Surg. 2004;114(5):1280-8; discussion 1289-91.        [ Links ]

2. Romundstad L, Breivik H, Roald H, Skolleborg K, Romundstad PR, Stubhaug A. Chronic pain and sensory changes after augmentation mammoplasty: long term effects of preincisional administration of methylprednisolone. Pain. 2006;124(1-2):92-9.        [ Links ]

3. Wilder-Smith OH, Arendt-Nielsen L. Postoperative hyperalgesia: its clinical importance and relevance. Anesthesiology. 2006;104(3):601-7.        [ Links ]

4. Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth. 2008;101(1):77-86.        [ Links ]

5. Chaparro LE, Giraldo N, Pabón LF, Agudelo S, Castillo JM, Gómez I. Efectividad de la ketamina para reducir los requerimientos perioperatorios de opioides. Rev Col Anest. 2005;33(3):169-74.        [ Links ]

6. De Kock MF, Lavand'homme PM. The clinical role of NMDA receptor antagonists for the treatment of postoperative pain. Best Pract Res Clin Anaesthesiol. 2007;21(1):85-98.        [ Links ]

7. Woolf CJ. Central sensitization: uncovering the relation between pain and plasticity. Anesthesiology. 2007;106(4):864-7.        [ Links ]

8. Bell RF, Dahl JB, Moore RA, Kalso E. Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev. 2006(1):CD004603.        [ Links ]

9. Poleshuck EL, Katz J, Andrus CH, Hogan LA, Jung BF, Kulick DI, et al. Risk factors for chronic pain following breast cancer surgery: a prospective study. J Pain. 2006;7(9):626-34.        [ Links ]

10. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006;367(9522):1618-25.        [ Links ]

11. Nienhuijs S, Staal E, Strobbe L, Rosman C, Groenewoud H, Bleichrodt R. Chronic pain after mesh repair of inguinal hernia: a systematic review. Am J Surg. 2007;194(3):394-400.        [ Links ]

12. Tebbetts JB. Achieving a predictable 24-hour return to normal activities after breast augmentation: part I. Refining practices by using motion and time study principles. Plast Reconstr Surg. 2002;109(1):273-90; discussion 91-2.        [ Links ]

13. Gryskiewicz JM. Avoiding pain and suffering after breast augmentation. Plast Reconstr Surg. 2002;110(7):1812-3.        [ Links ]

14. Fukami Y, Terasaki M, Okamoto Y, Sakaguchi K, Murata T, Ohkubo M, et al. Efficacy of preoperative dexamethasone in patients with laparoscopic cholecystectomy: a prospective randomized double-blind study. J Hepatobiliary Pancreat Surg. 2009;16(3):367-71.        [ Links ]

15. Jokela RM, Ahonen JV, Tallgren MK, Marjakangas PC, Korttila KT. The effective analgesic dose of dexamethasone after laparoscopic hysterectomy. Anesth Analg. 2009;109(2):607-15.        [ Links ]

16. Koc S, Memis D, Sut N. The preoperative use of gabapentin, dexamethasone, and their combination in varicocele surgery: a randomized controlled trial. Anesth Analg. 2007;105(4):1137-42, table of contents.        [ Links ]