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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.55 no.2 Campinas Mar./Apr. 2005
Multimodal analgesia in outpatient videolaparoscopic gynecologic surgery. Comparison between parecoxib and tenoxicam*
Analgesia pos-operatoria multimodal en cirugía ginecológica videolaparoscópica ambulatorial. Comparación entre parecoxib y tenoxican
Sérgio D. Belzarena TSA, M.D.I; Mozart T. Alves, M.D.II; Máximo L. D. Cucco, M.D.II; Vanius D. D'Ávila, M.D.II
IICirurgião Especialista em Videolaparoscopia
BACKGROUND AND OBJECTIVES: The quality
of postoperative analgesia in patients submitted to outpatient videolaparoscopic
gynecologic surgery was evaluated by comparing the effects of intravenous parecoxib
and tenoxicam in a double-blind study.
METHODS: Participated in this prospective study 60 patients who were randomly divided into two groups. All patients were premedicated with midazolam and one group (P) received 40 mg parecoxib before surgery. The other group (T) received 20 mg tenoxicam in the same manner. Spinal anesthesia with bupivacaine and sufentanil was administered for videolaparoscopic gynecologic procedures. Postoperative analgesia was evaluated using verbal and visual scales. Pain site (incisional, visceral or shoulder), supplemental analgesics and side effects were recorded, in addition to patients' satisfaction with the technique.
RESULTS: Analgesic quality was excellent with 76% Group P patients and 83% group T patients with no postoperative pain complaint or analgesic request. There were no statistical differences between groups in all evaluated criteria. Pruritus, although brief and mild, was the primary side effect. All patients were satisfied or very satisfied with the technique.
CONCLUSIONS: Multimodal analgesia with subarachnoid local anesthetic and opioid associated to intravenous NSAID produces excellent postoperative pain relief with few adverse effects in outpatient videolaparoscopic gynecologic surgery. The choice of the NSAID seems to be of minor importance for such results.
Key words: ANALGESICS, Anti-inflammatory non hormonal: parecoxib, tenoxicam, ANESTHESIA, Spinal block; SURGERY, Outpatient
JUSTIFICATIVA Y OBJETIVOS: Evaluar las
características de la analgesia pos-operatoria en pacientes sometidas a cirugía
ginecológica videolaparoscópica ambulatorial, comparando el efecto de parecoxib
y tenoxican venoso en un estudio doblemente encubierto.
MÉTODO: Fueron estudiadas prospectivamente 60 pacientes divididas de forma aleatoria en 2 grupos. Todas recibieron sedación pre-operatoria con midazolan. Un de los grupos (P) recibió antes de iniciar la cirugía 40 mg de parecoxib y en el otro (T) 20 mg de tenoxican. En la sala de operación fue hecha raquianestesia con bupivacaína y sufentanil. La analgesia pos-operatoria fue evaluada mediante la intensidad del dolor con escalas verbal y visual, localización del dolor (incisional, visceral, en el hombro) y el consumo de analgésicos suplementares. Fueron registrados los efectos colaterales adversos La satisfacción de la paciente con la técnica fue pesquisada.
RESULTADOS: La calidad analgésica fue excelente, con 76% de las pacientes del grupo P y 83% de las pacientes del grupo T sin queja de dolor y tampoco el uso de analgésicos en el pos-operatorio. No hubo diferencia entre los grupos en todos los criterios y períodos de evaluación analgésica. La incidencia de efectos adversos fue pequeña, no obstante, prurito de intensidad leve y de corta duración ocurrió frecuentemente. Todas las pacientes quedaron satisfechas o también muy satisfechas con la técnica empleada.
CONCLUSIONES: Una técnica de analgesia multimodal, con un componente de anestésico local y opioide por vía subaracnóidea asociado con AINE venoso produce analgesia pos-operatoria de excelente calidad con pocos efectos colaterales adversos en cirugía videolaparoscópica ginecológica ambulatorial. La elección del AINE no parece importante para la obtención de estos resultados.
The definition of the presence of two cycloxygenase enzyme isoforms, one primarily constitutional (isoform 1 or COX-1) and the other primarily inflammation-induced (isoform 2 or COX-2) has allowed the development of drugs preferably inhibiting the former, the latter or both. Since it is accepted that COX-1 plays important physiological role in renal, platelet and gastric function, specific COX-2 inhibitors would be more beneficial for patients needing acute or chronic anti-inflammatory drugs 1-3.
Parecoxib is a specific COX-2 inhibitor with pharmacological and pharmacokinetic profile which may be useful in Anesthesia. The possibility of intravenous administration is one of its advantages 4,5.
Among drugs available for a long time, tenoxicam is a non-specific cycloxygenase inhibitor which may be also intravenously administered and is used for postoperative analgesia 6,7.
This study aimed at comparing analgesic action and adverse effects of preoperative parecoxib or tenoxicam in patients submitted to outpatient gynecologic videolaparoscopy with multimodal postoperative analgesia.
After the hospital's Ethics Committee approval (Centro Hospitalar Santanense) and their informed consent, participated in this study 60 patients scheduled for outpatient gynecologic videolaparoscopy. Exclusion criteria were diabetes, renal or GI diseases or changes in platelet number or function, in addition to those having used NSAIDs.
Anesthesia was performed under typical monitoring: ECG, SpO2 and automatic noninvasive blood pressure. Patients were premedicated with 2 to 3 mg intravenous midazolam. Next, 40 mg parecoxib or 20 mg tenoxicam were administered in a double-blind manner. Drugs were administered by a nurse 5 minutes before referring patients to the operating room and according to instructions in an envelope indicating the NSAID as from a computer-generated list.
Spinal anesthesia was performed in the operating room with the patient in the lateral position with 27G needle and 15 mg of 0.5% hyperbaric bupivacaine plus 5 µg sufentanil. When sedation was insufficient, 1 to 2 mg intravenous midazolam were administered.
Procedures included videolaparoscopic salpyngectomy, oophoroplasty, miomectomy and adherences lysis and excluded exclusively diagnostic procedures.
Postoperative pain evaluation included site (shoulder, incision or visceral) and intensity. Intensity was evaluated by a verbal scale with 5 words: absent, mild, moderate, severe and very severe, and by 100 mm visual analog scale.
Postoperative pain was evaluated 30, 120 and 240 minutes after admission to the recovery room, before hospital discharge and 48 hours after the procedure.
Pain was initially treated with intravenous dipirone (1 g) and, if necessary, with intravenous fentanyl (25 µg). Nausea and vomiting were initially treated with intravenous metochlopramide (10 mg) and, when necessary, with 4 mg intravenous ondansetron. Doses and time for any postoperative drug were recorded.
Local or systemic adverse effects were investigated until hospital discharge, and then at 48 hours when patients returned to be evaluated by the surgeon.
Level of satisfaction with the technique was evaluated 48 hours after surgery by a scale with the following statements: not satisfied, moderately satisfied, satisfied, very satisfied.
Student's t test was used for continuous measurements and Mann-Whitney's U test for interval measures (ordinal data). Chi-square test was used for categorical data. p values below 0.05 were considered significant.
There were no differences between groups in demographics or type of surgery (Table I).
Most patients had no pain during the evaluation period. There have been no differences between groups, and 23 (76%) group P and 25 (83%) group T patients have not referred pain or requested supplemental analgesics. Among patients referring pain (7 in group P and 5 in group T) most of them related having shoulder pain but no one referred incisional pain. Verbal and visual scale evaluation has shown that there were no patients referring pain 30 minutes after PACU arrival, and that pain was predominantly mild or moderate at 120 minutes, decreasing at 240 minutes. There were no differences between groups in pain intensity or supplemental analgesics (Table II and Table III).
There has been high incidence of pruritus and low incidence of nausea and vomiting, without differences between groups (Table IV).
Patients' satisfaction with the technique has only included the words satisfied and very satisfied, without differences between groups.
Our two major results have shown no significant difference in postoperative analgesia with parecoxib or tenoxican for gynecologic procedures, and that multimodal analgesia has been an adequate technique.
There are several pharmacological differences between parecoxib and tenoxicam, among them duration of action (longer for tenoxicam), and specificity for cycloxygenase isoforms blockade (equal for COX-1 and COX-2 for tenoxicam). So, there would be advantages for parecoxib, which is a specific inhibitor of the inflammation-induced isoform, in a procedure where drug effect duration would not be of primary importance. Nevertheless, there were no diffe- rences between groups. This could have been due to the association of subarachnoid local anesthetic and opioid (postoperative multimodal analgesia) or to the fact that pain control requires the blockade of both cycloxygenase isoforms 8,9.
Pain after gynecologic videolaparoscopies is a major problem because these are outpatient procedures 10. Salpyngectomy has been particularly defined as painful and several alternatives have been proposed such as Hulka's clip or Yoong's ring. However, tube removal seems to be more effective when the aim is patient's sterilization 11-13. The above-mentioned studies have used general anesthesia and our data show that spinal anesthesia was an essential component for the analgesic result. The initial result (all patients referring "no pain" at 30 minutes) may be attributed to residual spinal anesthesia. Since there is another study showing that spinal anesthesia is more convenient for this type of surgery, our results suggest that this could be the technique or choice for this situation 14. Similarly, in this latter study, 75% of spinal anesthesia patients have not requested postoperative analgesics, as compared to 25% of general anesthesia patients 14.
Multimodal analgesia technique attempts to add beneficial effects of analgesics acting in different sites as well as to decrease the incidence of adverse effects. This technique combining bupivacaine's spinal effect, sufentanil's spinal and systemic effect, and peripheral and central effects of cycloxygenase inhibitors has proven to be effective for postoperative pain relief, but further evaluations with a larger number of patients are needed to determine whether other benefits of multimodal techniques are also observed 15,16.
A critic to our methodological design might be the absence of a placebo group. There are however several publications confirming higher analgesic quality and decreased opioid consumption when NSAIDs are administered. Most studies comparing parecoxib or tenoxicam to placebo have concluded that patients receiving NSAIDs have better postoperative analgesia 4-7 and this was the reason for not including a placebo group in our study.
No adverse effects related to NSAIDs used in this group of patients were observed although the power of our study was not sufficient for this type of observation, since a much larger number of participants would be necessary to determine the incidence and relate it to parecoxib or tenoxicam. Among few observed side effects, pruritus was present in more than 50% of patients (34 out of 60, 16 in group P and 18 in group T without difference). It was always mild or moderate lasting no more than 2 hours and needing no treatment for its reversion. For its characteristics, it could only be attributed to sufentanil administered for spinal anesthesia.
The incidence of nausea (1 group P and 2 group T patients) and vomiting (4 group P and 3 group T patients) was low as compared to other studies with this type of surgery however under general anesthesia 17,18. Whether spinal anesthesia was important to decrease these complications could not be assessed with the number of evaluated patients. Since nausea and vomiting are very distrurbing complication in outpatient procedures, further studies are needed. However, it is known that regional anesthesia is a factor to decrease such adverse effects 14,19. An animal study has suggested that the vomiting center is influenced by prostaglandins and that COX inhibitors have anti-emetic action 20.
In conclusion, postoperative analgesia for outpatient gynecologic videolaparoscopies with this multimodal technique including subarachnoid local anesthetics and opioids, and systemic NSAIDs, is adequate with most patients without pain complaint or requesting additional analgesics. There were few side effects which have not interfered with the outpatient character of the procedure. The choice of the NSAID, specific for COX-2 inhibition (parecoxib) or nonspecific (tenoxicam) was irrelevant.
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Dr. Sérgio D. Belzarena
Address: Rua José Américo Domingues 96
ZIP: 97574-710 City: Livramento, Brazil
Submitted for publication July 12, 2004
Accepted for publication November 12, 2004
* Received from Serviço de Anestesiologia do Centro Hospitalar Santanense, Livramento, RS