Journal of Clinical Anesthesia (2015) xx, xxx–xxx

Original Contribution

Remifentanil versus fentanyl in total intravenous anesthesia for lumbar spine surgery: a retrospective cohort study☆ Berlet Thomas MD ⁎ Gemeinschaftskrankenhaus Herdecke, Department of Anesthesia, Gerhard-Kienle-Weg 4, Herdecke 58313, Germany Received 29 April 2013; revised 14 August 2014; accepted 26 March 2015

Keywords: Anesthesia; Intravenous; Outcome assessment; Spine/surgery

Abstract Study objective: The aim of this study was to compare the speed of anesthetic recovery and the perioperative analgesic requirements in patients who received total intravenous anesthesia (TIVA) with either remifentanil-propofol or fentanyl-propofol for lumbar spine surgery. Design: Retrospective cohort study. Setting: Operating room, postanesthesia care unit, and general surgical ward. Patients: One hundred six patients (53 in each group) with American Society of Anesthesiologists status I, II, or III who received either remifentanil-propofol TIVA or fentanyl-propofol TIVA for elective lumbar vertebral disc surgery. Measurements: Patient demographics, total duration of anesthesia relative to surgical duration, time to emergence from anesthesia after completion of surgery, length of stay in the postanesthesia care unit, and requirements for opioid analgesia, nonopioid analgesia, and antiemetics in the perioperative period. Main results: No differences in anesthesia time, emergence time, or length of stay in the postanesthesia care unit were found between the remifentanil-propofol and fentanyl-propofol groups. Postoperative opioid and nonopioid analgesic use was significantly higher in the remifentanil-propofol group. Conclusions: Remifentanil and fentanyl are equally efficient with regard to the speed of patient turnover when used as part of TIVA for lumbar disc surgery, but remifentanil use is associated with increased perioperative analgesic requirements. © 2015 Elsevier Inc. All rights reserved.

1. Introduction Lumbar spinal surgery is the most frequently performed type of neurological surgery [1]. Given the elective nature and predictable surgical course of this type of procedure, ☆

Disclosures and conflict of interest: none declared. ⁎ University Hospital Bern, Department of Intensive Care Medicine, Bern 3010, Switzerland. Tel.: +41 31 6325078; fax: +41 31 6329644. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.jclinane.2015.03.024 0952-8180/© 2015 Elsevier Inc. All rights reserved.

operating schedules are usually busy, and short turnover times are required for optimized operating room use. Operating room efficiency is governed by a number of factors, two of which are anesthesia-controlled time and turnover time. Anesthetic techniques providing fast emergence from anesthesia after the completion of surgery may contribute to the shortening of anesthesia-controlled time [2]. Total intravenous anesthesia (TIVA) incorporating the combined use of propofol and remifentanil has been shown to provide faster emergence than other anesthetic techniques

2 [3]. However, it remains debatable whether the time savings observed in some controlled clinical studies translates into clinically relevant benefits [4]. A modification of our departmental anesthetic approach to lumbar spine surgery was prompted by an awareness of the lack of evidence for the superiority of remifentanilpropofol TIVA (REMI-TIVA) over fentanyl-propofol TIVA (FENT-TIVA) [3]. This shift offered an opportunity to study the efficacy of remifentanil infusion versus fentanyl boluses as part of a TIVA regimen for elective lumbar spine surgery. To this end, we conducted a retrospective cohort study of patients who underwent lumbar vertebral disc surgery before and after the changeover from one anesthetic regimen to the other. The following parameters were evaluated: (a) total duration of anesthesia relative to surgical duration, (b) time to emergence from anesthesia after the completion of surgery, (c) length of stay in the postanesthesia care unit (PACU), and (d) requirements for opioid analgesia, nonopioid analgesia, and antiemetics in the perioperative period.

2. Materials and methods 2.1. Patient selection Patients who underwent lumbar vertebral disc surgery from July 2008 to September 2008, when remifentanil was routinely used as part of the anesthetic regimen, were compared with an identical number of consecutive patients from a period commencing in July 2009, when fentanyl was part of the routine anesthetic regimen. Inclusion criteria were recorded International Classification of Diseases code M51 (“other intervertebral disc disorders”) [5] and all of the following procedural codes: “surgical access to the lumbar spine,” “vertebral disc surgery,” and “microsurgical technique”; the use of propofol as the only hypnotic; and the use of either remifentanil or fentanyl as the only narcotic for anesthetic induction and maintenance. Exclusion criteria were nonelective surgery, redo surgery, American Society of Anesthesiologists (ASA) physical status IV or higher, and incomplete anesthetic records. The ethics committee (Ethik-Kommission der Aerztekammer Westfalen-Lippe, Muenster, Germany) waived the requirement for informed consent.

2.2. Induction and maintenance The general anesthetic approach consisted of intravenous induction with propofol and either remifentanil or fentanyl, endotracheal intubation facilitated by nondepolarizing muscle relaxants, and mechanical ventilation with oxygen/ air to maintain normocapnia. Propofol and remifentanil were delivered as continuous infusions with additional boluses as required via manually controlled infusion pumps.

B. Thomas The typical dosage ranges for maintenance of anesthesia were 4 to 6 mg kg−1 h−1 for propofol and 0.25 μg kg−1 min− 1 for remifentanil. Delivery of anesthetic medication was stopped upon completion of surgical skin closure. Fentanyl was administered as boluses in the range of 1 to 3 μg/kg for both induction and maintenance. The timing of repeat doses of fentanyl was at the discretion of the attending anesthesiologist. No muscle relaxants were given intraoperatively. Neither intraoperative cerebral monitoring nor intraoperative wake-up tests were performed. Transitional analgesia consisted of a nonopioid analgesic (paracetamol or metamizole) and piritramide. They were given intravenously 15 minutes before the anticipated end of surgery; dosages were at the discretion of the attending anesthesiologist.

2.3. Recovery and postoperative period Discharge from the PACU was possible when the modified Aldrete score was at least 9 out of 10 points and patients had been assessed by the responsible neurosurgeon [6]. On the surgical ward, patients received regular oral ibuprofen or paracetamol and intravenous piritramide and metamizole as required, to achieve pain control to a level below 4 on a visual analog scale.

2.4. Data collection and statistical analysis The following data were extracted from the medical notes: patient age, sex, height, and weight; ASA status; surgical time (time from the skin incision to application of the surgical dressing); anesthesia time (time from induction of general anesthesia to removal of the endotracheal tube); emergence time (duration from application of the surgical dressing to arrival in the PACU); PACU time (time from PACU arrival until transfer to a surgical ward); the use of piritramide opioid analgesia (cumulative piritramide dose in milligrams), nonopioid analgesia (number of doses), and antiemetics (number of doses); need for reoperations; medical interventions indicative of the development of relevant postoperative complications delaying the hospital discharge. Body mass index (BMI) was calculated as weight/ height2. Our use of “perioperative” refers to the period from anesthetic induction until the morning following the day of the operation. Statistical analysis was performed using the StatPlus software package (AnalystSoft Inc., Alexandria, Virginia). Continuous data are presented as mean and SD. All tests of statistical significance were 2-sided. Student t test was used for the comparison of normally distributed continuous data, the Mann-Whitney test was used for the comparison of nonnormally distributed continuous data, and Fisher exact test was used for the comparison of categorical data. P values b .05 were considered statistically significant.

Remifentanil-TIVA versus fentanyl-TIVA in spine surgery

3. Results

T1

T2

F1

T3

Table 2

One hundred six patients (53 per group) were studied. There were no statistically significant differences in patient demographics (Table 1). Surgical times were significantly longer in the FENT-TIVA group, but anesthesia times were not. There were no differences between the remifentanil and fentanyl groups with regard to emergence times and PACU times (Table 2). The relationship between surgery times and anesthesia times was evaluated by regression analysis for both groups. The coefficients of determination were r2 = 0.675 for the REMI-TIVA group and r2 = 0.664 for the FENT-TIVA group (Figure). Patients in the REMI-TIVA group required significantly higher amounts of both opioid and nonopioid analgesics in the perioperative period. Opioid analgesia was mainly administered intraoperatively and in the PACU. A total of 112 doses of nonopioid analgesia were given to patients in the remifentanil group compared with a total of 82 doses in the FENT-TIVA group. The excess nonopioid administration in REMI-TIVA patients occurred in the wards and was statistically significant. In total, 37 doses of antiemetics were given to patients in the REMI-TIVA group compared with 32 doses in the FENT-TIVA group (n.s.) (Table 3). No patient required a reoperation or developed a postoperative complication delaying the hospital discharge.

4. Discussion The main finding of this study was that FENT-TIVA and REMI-TIVA were equivalent in terms of anesthesia time, the speed of emergence from anesthesia, and the subsequent length of stay in the PACU. Anesthesia time correlated with surgery time for both agents. Pain control was inferior in patients who received REMI-TIVA, but the use of antiemetics did not differ between the two types of TIVA. Numerous studies comparing remifentanil with other opioids as part of a general anesthesia have been published. However, these studies were very heterogeneous regarding the involved anesthetic regimens [3]. Outside of the cardiovascular surgery anesthesia field, only a small number of comparative studies have been published investigating Table 1

Patient characteristics

Age (y) Male/female (no.) BMI (kg × m−2) ASA physical status (I & II/III) (no.)

3

REMI-TIVA (n = 53)

FENT-TIVA (n = 53)

P

55.5 (15.6) 31/22 27.1 (4.6) 48/5

53.4 (13.3) 29/24 27.7 (5.2) 48/5

.46 .69 .59 N .99

Values are means ± SD or number of patients (no.).

Procedure times and intervals

Surgery time (min) Anesthesia time (min) Emergence time (min) PACU time (min)

REMI-TIVA (n = 53)

FENT-TIVA (n = 53)

P

55.5 (15.9) 99.9 (18.8) 12.0 (5.1) 47.4 (20.7)

65.5 (25.5) 108.6 (27.7) 12.5 (9.1) 47.8 (25.2)

.016 .062 .762 .91

Values expressed are means ± SD.

remifentanil and fentanyl as components of true TIVA regimens. A literature search did not retrieve any studies performed in spinal surgery patients. Some investigators have reported shortened times to extubation with REMI-TIVA as opposed to FENT-TIVA. In a clinical study by Del Gaudio et al performed in patients undergoing supratentorial craniotomies, the time to extubation was shorter in the remifentanil group, but total anesthesia time was no different than that of the fentanyl group (252 vs 255 minutes, respectively) [7]. In a trial by Gaszynski et al involving patients undergoing bariatric surgery with procedure times of approximately 157 minutes, the time to extubation was reduced by less than 2 minutes with the use of remifentanil [8]. In a study of patients undergoing oral surgery by Takayama et al, the time to extubation was 3 minutes less in the remifentanil group; overall anesthesia time, however, it was 12 minutes longer in the remifentanil group [9]. In a clinical trial by Coskun et al performed in patients undergoing septorhinoplasty, patients who received remifentanil were extubated just under 3 minutes earlier than patients who received fentanyl. However, fentanyl was delivered as a fixed-rate infusion until the end of surgery in this study [10]. This appears an uncommon dosage regimen for procedures of short duration and is likely to have introduced a degree of bias in favor of remifentanil. In a trial involving patients undergoing carotid endarterectomy by Kostopanagiotou et al, the time to extubation was reduced by just over 2 minutes in the remifentanil group, but overall anesthesia times exceeded 2 hours and did not significantly differ between the groups [11]. In contrast to these favorable results for remifentanil, some investigators have found identical emergence times for fentanyl and remifentanil: Horrichs-Haermeyer et al prospectively studied patients undergoing gynecological laparoscopy [12], Nakada et al studied patients undergoing breast surgery [13], and Twersky et al studied a variety of abdominal and superficial procedures [14]. In summary, studies of emergence and anesthesia times comparing REMI-TIVA and FENT-TIVA show equipoise. The findings of this study are in agreement. A number of investigators have reported favorable PACU characteristics of remifentanil, such as the time to reach normal Aldrete scores [7,15]. However, in analyses of TIVA regimens that include the length of PACU stay as part of their evaluation, no statistically significant difference was found

B. Thomas

Anesthesia time [minutes]

4 200

Anesthesia time = 46.1 + .97 * surgery time (REMI-TIVA)

180

Anesthesia time = 50.6 + .89 * surgery time (FENT-TIVA)

160 140 120 100

REMI-TIVA

80

FENT-TIVA

60 40 20 0 0

20

40

60

80

100

120

140

Surgery time [minutes]

Figure Regression analysis of surgery time as the explanatory variable and anesthesia time as the response variable for REMI-TIVA and FENT-TIVA.

with remifentanil compared with fentanyl [8,10,11,14], which is in accordance with our study. The higher requirement for opioid and nonopioid analgesia found in our study's remifentanil group, particularly in the early postoperative stages, illustrates the limited capability of remifentanil-based TIVA in controlling postoperative pain in spine surgery. As the analgesic effect of piritramide administered in the early postoperative stages diminished, patients requested additional analgesia in the wards. Most other studies suitable for comparison have reported identical levels of postoperative pain with remifentanil and fentanyl [7,9,11,12,14,16]. However, none of these studies were performed in musculoskeletal surgery patients. Studies assessing surgical procedures causing a similar degree of postoperative pain to lumbar spine surgery have reported higher levels of postoperative pain after the use of remifentanil [8,10]. Table 3 Perioperative opioid analgesia, nonopioid analgesia, and antiemetic requirements REMI-TIVA FENT-TIVA P (n = 53) (n = 53) Piritramide (mg) Total perioperative 17.4 ± 10.4 Intraoperative 7.3 ± 3.4 PACU 5.1 ± 6.2 Ward 5.1 ± 6.7 Nonopioid analgesia (no. of doses) Total perioperative 2.1 ± 1.1 Intraoperative 0.9 ± 0.2 PACU 0.1 ± 0.2 Ward 1.1 ± 1.1 Antiemetics (no. of doses) Total perioperative 0.7 ± 0.9 Intraoperative 0.6 ± 0.8 PACU 0.1 ± 0.3 Ward 0.1 ± 0.2 Values expressed are means ± SD.

7.2 ± 7.3 0.3 ± 1.4 1.8 ± 3.8 5.1 ± 6.4

b .0001 b .0001 .008 .94

1.6 ± 1.0 0.9 ± 0.4 0.0 ± .0.1 0.7 ± 0.9

.0064 .4 .73 .03

0.6 ± 0.7 0.5 ± 0.6 0.0 ± 0.0 0.1 ± 0.3

.79 .76 .62 .61

Antiemetic use was considerable in this study, suggesting a clinically significant incidence of postoperative nausea, although no conclusions can be drawn regarding the frequency of vomiting because this information was not available from the medical notes. Assuming that perioperative opioid analgesia contributed to perioperative nausea and vomiting, one would expect to find lower antiemetic use in the fentanyl group, which was not the case. The absence of a statistically significant difference in postoperative nausea is in agreement with most comparable studies [7,12–14]. This comparative study of TIVA regimens in spinal surgery offers insight into the perioperative course of this type of procedure, particularly regarding indicators of anesthetic regimen efficacy (ie, emergence and PACU times) and resource use in perioperative care (reflected by the frequency of patients' requests for rescue analgesia and antiemetics). What is the likely explanation for the observed nonsuperiority of REMI-TIVA in terms of emergence and PACU times, and what conclusions can be drawn from this? The characteristic features of lumbar vertebral disc surgery relevant to the anesthesiologist are the short procedure duration, the necessity for prone positioning along with strict avoidance of spontaneous patient movements until the end of the procedure, and the need to control postoperative pain. These features require the maintenance of deep anesthesia until repositioning of the patient after surgery is completed. Transitional opioid analgesia is usually required unless residual analgesic effects of the opioids used for anesthesia are present at the time of emergence. Under these circumstances, the potential pharmacological advantages of remifentanil do not appear to translate into clinically relevant benefits. It is conceivable that the use of transitional opioid analgesia could have delayed patients in the REMI-TIVA group from reaching readiness for transfer from the PACU to the surgical ward. However, the piritramide doses used were not excessive. On average, 17 mg of piritramide was given to patients in the remifentanil group. This is equivalent to just over 10 mg of morphine [17].

Remifentanil-TIVA versus fentanyl-TIVA in spine surgery

5

This retrospective study could be criticized for not addressing possible confounding factors. Could the observation of identical emergence characteristics between the groups have been caused by factors unaccounted for in the study (eg, ancillary medications)? Given the stringent inclusion criteria and the fact that patient demographics were well balanced between the groups, it appears unlikely that other factors, such as the preoperative use of opioid analgesics, would have influenced the outcome parameters. We did not attempt to compare costs of each technique, as the direct costs of consumables to the institution are generally low and the prices of fentanyl, propofol, and particularly remifentanil have decreased substantially in recent years due to the availability of generics.

[5] World Health Organisation. ICD-10: International statistical classification of diseases and related health problems. 10th revision, ed. 2010. Geneva: World Health Organisation; 2004. [6] Aldrete JA. The post-anesthesia recovery score revisited. J Clin Anesth 1995;7:89-91. [7] Del Gaudio A, Ciritella P, Perotta F, Puopolo M, Mastronardi P, De Vivo P. Remifentanil vs fentanyl with a target controlled propofol infusion in patients undergoing craniotomy for supratentorial lesions. Minerva Anestesiol 2006;72:309-19. [8] Gaszynski TM, Strzelczyk JM, Gaszynski W. Post-anaesthesia recovery after infusion of propofol with remifentanil or alfentanil or fentanyl in morbidly obese patients. Obes Surg 2004;14:498-504. [9] Takayama A, Yamaguchi S, Ishikawa K, Shinozaki M, Kimura Y, Nagao M, et al. Recovery of psychomotor function after total intravenous anaesthesia with remifentanil-propofol or fentanyl-propofol. J Anesth 2012;26:34-8. [10] Coskun D, Celebi H, Karaca G, Karabiyik L. Remifentanil versus fentanyl compared in a target-controlled infusion of propofol anaesthesia: quality of anaesthesia and recovery profile. J Anesth 2010;24:373-9. [11] Kostopanagiotou G, Markantonis SL, Polydorou M, Pandazi A, Kottis G. Recovery and cognitive function after fentanyl or remifentanil administration for carotid endarterectomy. J Clin Anesth 2005;17:16-20. [12] Horrichs-Haermeyer G, Stute P, Reif H, Soukup J, Sabatowski R, Grond S. Cognitive function and reaction time after remifentanilpropofol or fentanyl-propofol anaesthesia for gynaecological laparoscopy. Anaesth Intensive Med 2002;43:517-23. [13] Nakada T, Ikeda D, Yokota M, Kawahara K. Analysis of the costeffectiveness of remifentanil-based general anaesthesia: a survey of clinical economics under the Japanese health care system. J Anesth 2010;24:832-7. [14] Twersky RS, Jamerson B, Warner DS, Fleisher LA, Hogue S. Hemodynamics and emergence profile of remifentanil versus fentanyl prospectively compared in a large population of surgical patients. J Clin Anesth 2001;13:407-16. [15] Lacombe GF, Leake JL, Clokie CM, Haas DA. Comparison of remifentanil with fentanyl for deep sedation in oral surgery. J Oral Maxillofac Surg 2006;64:215-22. [16] Naito A, Endo T, Inoue J, Okuno S, Uchida O, Kawahara R. Comparative study of anaesthesia with remifentanil vs fentanyl in terms of postoperative pain and shivering. Masui 2009;58:77-80. [17] Bouillon T, Kietzmann D, Port R, Meineke I, Hoeft A. Population pharmacokinetics of piritramide in surgical patients. Anesthesiology 1999;74:7-15.

5. Conclusions Remifentanil-propofol TIVA and FENT-TIVA are equally efficient for lumbar disc surgery, but the use of remifentanil requires increased perioperative analgesic use.

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Remifentanil versus fentanyl in total intravenous anesthesia for lumbar spine surgery: a retrospective cohort study.

The aim of this study was to compare the speed of anesthetic recovery and the perioperative analgesic requirements in patients who received total intr...
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