Postthyroidectomy pain control using ropivacaine wound infiltration after intraoperative remifentanil: A prospective double blind randomized controlled study

Methods Fifty elective ASA I–II patients scheduled for thyroid surgery were included in this study. Balanced anesthesia was performed with propofol, remifentanil, N 2 O, isoflurane. Patients were randomized in two equal groups: ropivacaine ( n = 25) and saline ( n = 25) which respectively had end-of-surgery wound infiltration with 15 ml of ropivacaine 2% or the same volume of saline. Results Pain intensity, morphine requirement and the length of stay in PACU were significantly lower in ropivacaine group as compared to saline group ( P < 0.05). No difference was observed in the surgical ward. Conclusions If remifentanil is used for intraoperative analgesia, end-of-surgery wound infiltration with 15 ml ropivacaine 2% is an efficient strategy to control postthyroidectomy pain. Keywords Thyroid surgery Ropivacaine Wound infiltration 1 Introduction Although thyroid surgery is usually rated as moderately painful, postoperative pain control frequently requires intravenous opioid [1,2] . Several analgesic regiments including locoregional analgesia, part of a multimodal approach, have been reported to be effective for postthyroidectomy pain control [3–6] . Remifentanil is a powerful ultra-short duration opioid, recently introduced, and almost free from any residual analgesic effect. It therefore requires anticipation of pain on emergence from anaesthesia and early treatment of postoperative pain by using i.v. morphine. Because real intensity of postoperative pain after thyroid surgery remains debated and clear efficiency of end-of-surgery wound infiltration with local anesthetic solution has not been demonstrated, we conducted a prospective double blind randomized study evaluating ropivacaine end-of-surgery wound infiltration for pain relief after thyroid surgery. 2 Methods 2.1 Patients After ethics committee approval and informed consent, 50 ASA I–II patients with normal thyroid function or in a euthyroid state scheduled for partial or total thyroid surgery under general anesthesia were enrolled into the study. At the preoperative visit patients were instructed about the study design, especially to rate pain intensity (none: 0 and worth: 100) and satisfaction (worth: 0 and best: 100) using a 100 mm Visual Analogue Scale (VAS P and VAS S , respectively). Patients were excluded if they had any preoperative analgesic medication or corticosteroid drug. 2.2 Anesthetic management A single senior surgeon performed all surgical interventions between 8:30 and 12:30 a.m. One hour before arrival in the operating theatre patients were premedicated with hydroxyzine p.o. 50 mg. After induction of anesthesia (bolus doses of propofol 2–3 mg/kg and remifentanil 0.5 μg/kg) tracheal intubation was performed, anesthesia was maintained with an inhalational mixture (50% 02/N20, and 0.6–0.9% isoflurane) and an infusion of remifentanil 0.05–1 μg/(kg min) titrated to maintain preinduction heart rate and blood pressure within a ±20% range. At the end-of-surgery, just before wound closure, 1 g of i.v. paracetamol was administered and the patients were randomized according to a computerized list of random numbers into two groups. Fifteen millilitres of solution using either ropivacaine 2% (R), or saline (S) was used for homogenous infiltration by the surgeon of the subcutaneous wound sides. The randomization procedure was supervised by a staff anesthesiologist not directly involved in patient care, however in case of emergency, all physicians in charge of the patients including those in the postoperative care unit and in the surgical ward could access the procedure on demand. Remifentanil infusion was maintained until the last surgical stitch and patients were allowed weaning from mechanical ventilation and extubation was performed in the operating room following a standardized procedure. 2.3 Measurements The total amount of anesthetic agents required for surgery was calculated and the following parameters were collected: duration of surgery, delay to extubation defined as the time elapsing termination of the infusion of remifentanil to extubation, titration delay defined as the time elapsing tracheal extubation and first administration of i.v. morphine. In PACU where patients were asked to score their pain intensity using VAS P . The staff (physician and nurses) blinded to randomization followed a specific postoperative pain management procedure using i.v. morphine titrated on pain intensity measurement. If VAS P ≥ 40 mm, intravenous morphine was injected every 5 min in 2 mg increments and pain intensity was reassessed every 5 min until pain relief arbitrary defined by VAS P < 40 mm. For each patient the following parameters were recorded in PACU: maximum VAS P at rest, the necessity to titrate morphine, the amount of morphine and the duration of titration required to reach VAS P < 40 mm at rest. Ramsay sedation scale was used to rate daytime sedation intensity [7] before each VAS P evaluation. Discharge of the patient from PACU was decided according to the following criteria: achieved Aldrete score of 10 [8] , adequate pain relief (visual analog scale < 3/10), absence of nausea and/or vomiting and absence of surgical complication (such as bleeding). The incidence of nausea and vomiting and the length of stay in PACU were also collected. In the surgical ward, pain VAS was measured every 4 h during the first 24 postoperative hours and i.v. paracetamol injections were repeated systematically every 6 h. Subcutaneous morphine (5–10 mg) was injected if rest VAS P > 40 mm. For each patient, maximum postoperative VAS P (including dynamic pain during a swallowing or coughing effort), the necessity of additional subcutaneous morphine and its amount and the incidence of opioid related side effects (nausea, vomiting), and daytime sedation scale were noted for the first 24 postoperative hours in the surgical ward starting immediately after arrival from PACU. Blinded overall satisfaction's evaluation of postoperative pain management (VAS S ) was conducted the last day of the hospital stay. 2.4 Statistics The sample size of each group was calculated to obtain a mean difference in the immediate postoperative VAS P of 30 mm with a power of 0.8. A P value of 0.05 was considered significant. Data were analysed using Jandel Sigma Stat statistical software (USA). With regard to distribution, Student's t test or Mann and Whitney rank sum test was used for comparisons between groups. 3 Results All patients completed the study. No significant difference was observed between R and S patient's demographic and intraoperative characteristics ( Table 1 ). In PACU, VAS P was significantly lower in R as compared to S. Patients of S received more morphine, and sustained a longer duration of titration as compared to R ( Table 2 ). The length of stay in PACU was significantly shorter in R as compared to S (106 ± 37 and 147 ± 33 min). In the surgical ward morphine consumption, incidence of nausea and vomiting, daytime sedation ratings and overall VAS S were similar in both groups ( Table 3 ). 4 Discussion We demonstrated that end-of-surgery wound infiltration reduced initial postthyroidectomy pain intensity and produced opioid sparing, resulting in shorter length of stay in PACU. To our knowledge the present study is the first report evaluating end-of-surgery wound infiltration with ropivacaine after remifentanil-based intraoperative analgesia in thyroid surgery patients. The justification of regional analgesia to control postthyroidectomy pain is debated. Bilateral deep cervical plexus block is not considered as a safe technique. Bilateral superficial cervical plexus blocks alone [6] cannot preclude the need for opioid analgesics in most patients. End-of-surgery wound infiltration is certainly an interesting strategy when included in a multimodal analgesic approach. It is a simple technique that was reported to lessen opioid consumption not only in thyroid surgery but also in other superficial and short-lasting procedures [9,10] . Our method has some limitations. It could be argued that differences in pain intensity we demonstrated between groups in the early postoperative period might have been erased if, as recommended by some authors [11,12] , intravenous morphine had been injected prior to continuous remifentanil infusion cessation. We agree that anticipation of pain relief using intraoperative morphine administration might have reduced early postoperative pain scores in both groups, but certainly induced confounding factors in the present case, rendering our treatment efficacy difficult to interpret. Moreover intraoperative morphine administration in anesthetized patients might have prolonged extubation and titration delays of our patients certainly resulting in a longer PACU stay in both groups. In the same way, we observed a larger proportion of patients given morphine titration in the ropivacaine group (20/25) in comparison with previous works that used local anesthetics wound infiltration or block techniques. Indeed, morphine titration was required in only one-third to half of postthyroidectomy patients after wound infiltration [13] or bilateral superficial cervical plexus blocks [6] . Because wound infiltration was scrupulously performed, step-by-step all around the incision banks, we assume that differences in opioid requirements between our observation and other similar studies are mostly related to intraoperative analgesic regiment. By using intraoperative remifentanil we certainly minimized the residual analgesic effect usually promoted by long or intermediate duration opioid resulting in more patients reaching 40 mm VAS pain score. Similarly, we measured more severe than attended pain intensities in the saline group as compared to analogous studies that have included a control group. Although remifentanil-induced opioid tolerance [14–16] appears unlikely, our study design promoting more intense than expected pain intensities, has potentially enhanced the efficiency of the wound infiltration. On the other hand, our methods allowed precise evaluation of postthyroidectomy pain intensity after intraoperative remifentanil administration and clearly demonstrated the efficiency of wound infiltration. We confirm that postthyroidectomy pain has not only a superficial component but also certainly a visceral part controlled by early low dosage morphine i.v. titration in PACU. In the conditions of our study, end-of-surgery wound infiltration shortened PACU morphine titration duration that was divided by two folds with a mean 31 min reduction in the length of PACU stay and earlier readiness to ward transfer. Although we did not perform a cost study we believe that the length of stay in PACU is an important clinical end-point especially in hospitals with high rate of turn over with a registration limiting the number of patients in charge per nurse. Interestingly, conscious morphine titration in PACU rather than morphine injection in anesthetized condition has probably enhanced postoperative pain intensity in both groups but certainly favoured low morphine consumption in the ward. Indeed, only few patients (5/50) required supplemental morphine in the ward. Our data suggest that remifentanil-based intraoperative analgesia associated with end-of-surgery wound infiltration followed by early PACU awake morphine i.v. titration is a satisfying strategy to control pain during thyroid surgery. In summary, end-of-surgery wound infiltration with 15 ml ropivacaine 2% significantly reduces immediate postoperative pain VAS, morphine requirements and PACU length of stay after thyroid surgery. 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