Comparison of fentanyl and morphine in intravenous patient controlled analgesia after open gastrectomy surgery

JOURNAL OF MEDICAL RESEARCH COMPARISON OF FENTANYL AND MORPHINE IN INTRAVENOUS PATIENT-CONTROLLED ANALGESIA AFTER OPEN GASTRECTOMY SURGERY Nguyen Toan Thang, Nguyen Huu Tu Department of Anesthesia and Critical Care, Hanoi Medical University A prospective and randomized study was conducted to assess the efficacy and adverse effects of a fentanyl intravenous patient - controlled analgesia (IV - PCA) compared with a morphine IV-PCA after open gastrectomy surgery Ninety patients were randomly allocated into two groups: Group F with a fentanyl concentration of 25 μg/mL, a bolus of 25 μg and a lockout time of 10 minutes and Group M with a morphine concentration of mg/ml, a bolus of mg and a lockout time of 10 minutes No background infusion was included in either group Pain severity was assessed by Visual Analogue Scale (VAS) at rest and on coughing, and the incidence of adverse effects was assessed postoperatively during the first 24 hours Group F showed significantly lower mean VAS scores at rest and on coughing compared to Group M The incidence of postoperative nausea and vomiting (PONV) in group M was 31.1% and in group F was 15.5%, p < 0.05 The incidence of pruritus in group M was 17.8% and in group F was 8.9%, p < 0.05 The incidence of patients reporting that they were very satisfied with their pain relief in Group F was higher than that in Group M (71.1% of patients in group F versus 51.1% of patients in group M, p < 0.05) No respiratory or cardiovascular complications were observed in either group The fentanyl IV - PCA is a more effective postoperative analgesia than the morphine IV - PCA, providing greater patient satisfaction and lower incidences of PONV and pruritus after open gastrectomy surgery Keywords: intravenous PCA, fentanyl, morphine, gastric surgery I INTRODUCTION Postoperative pain has substantial, physical and psychosocial effects on patients Insuf- and standard method of pain relief that allows patients to self - administer small preset ficient analgesia can thereby delay patient boluses recovery Although there has been increased conventional methods, IV - PCA provides understanding of the pathophysiology of pain of opioids In comparison with slightly better pain control and higher patient in recent years, as well as the recent develop- satisfaction In the United States, there are ment of improved pharmacology and analge- approximately 13 millions patients per year sic techniques, acute pain treatment after using this method to control acute pain [3; 4] surgery remains insufficient, even in devel- In Vietnam, IV - PCA with opioids has also oped countries [1; 2] Intravenous Patient- been widely adopted for postoperative pain Controlled Analgesia (IV - PCA) is a popular management Traditionally, morphine is the most commonly utilized opioid in this setting, yet studies providing evidence that morphine Corresponding author: Nguyen Toan Thang, Department of Anesthesia and Critical Care, Hanoi Medical University E-mail: thanggmhs@gmail.com Received: 20 October 2016 Accepted: 10 December 2016 88 is the preferred opioid for IV - PCAs are lacking In spite of having strong analgesic effects and being low - cost, morphine can cause respiratory depression and other JMR 105 E1 (7) - 2016 JOURNAL OF MEDICAL RESEARCH adverse effects such as deep sedation, who were scheduled for open gastrectomy nausea and vomiting, pruritus, and urinary surgery under general anesthesia were en- retention [1; 2] rolled in this study Patients were excluded if Fentanyl is a - amilidopiperidien com- they were younger than 18 years or older than pound with high lipid solubility, which greatly 80 years old, had a history of allergy to reduces the onset time of the analgesic effect opioids, had daily intake of opioids or other It takes 30 seconds for fentanyl to begin to analgesics, had known or suspected drug take effect, with its maximum effect reached addiction, or were unable to understand or use five minutes after administration Fentanyl is a visual analogue scale (VAS) and a patient- also a potent and ideal drug for IV - PCA, as controlled analgesia (PCA) device Patients its redistribution is rapid and wide with a short with severe renal and hepatic diseases were duration, and it does not produce the active also excluded metabolites that cause respiratory depression Study design [5, 6] Fentanyl is a µ opioid receptor agonist with several advantageous pharmacological characteristics, including strong analgesic effects (approximately 80 - 100 times more potent than morphine) and as mentioned above, a more rapid onset of action compared to morphine [7] Studies by Hutchison and Stavropoulou suggested that fentanyl, with its effective ability to relieve pain and its low A prospective and randomized study was carried out in the Anesthesia and Critical Care Department of Bach Mai University Hospital in Hanoi, Vietnam from October 2014 to November 2015 In this study, patients were blinded to their group assignment, which was undertaken using a sealed envelope technique (Group F, n = 45; Group M, n = 45) frequency of adverse effects such as postop- In the operating room, all patients were erative nausea and vomiting (PONV), pruritus monitored using electrocardiography (ECG), or urinary retention, might be more preferable noninvasive arterial blood pressure devices, than morphine for IV - PCA [8; 9] However, and oxygen saturation and end-tidal carbon little information in the literature has been re- dioxide measuring equipment Patients were ported regarding the analgesic efficacy and induced with mg/kg of intravenous (IV) adverse effects of the fentanyl IV - PCA [10] propofol After muscle relaxation had been This study was carried out to prospectively achieved by IV administration of 0.6 mg/kg compare the postoperative analgesic efficacy rocuronium and adverse effects of IV - PCAs using intubated fentanyl and morphine in patients who just started recently underwent open gastrectomy propofol infusion at a rate of - mg/kg/hour II SUBJECTS AND METHODS Subjects bromide, and the controlled Anesthesia was trachea was ventilation was maintained by and intermittent IV injection of fentanyl and rocuronium At the end of surgery, all patients received one gram of paracetamol Ninety patients with American Society of Intensities of postoperative pain at rest and Anesthesiologists (ASA) physical status I - II on active coughing were evaluated using a JMR 105 E1 (7) - 2016 89 JOURNAL OF MEDICAL RESEARCH VAS, from (“no pain”) to 10 (“the worst pain a respiratory rate of less than breaths per imaginable”) Adequate analgesia was defined minute was observed, the PCA pump was as VAS < at rest A Modified Ramsay stopped VAS at rest and on active coughing, Sedation Scale (from to 6), where is any incidence of PONV, and the patient’s anxious or restless or both and is no Ramsay scale were recorded at 2, 6, 12 and response to stimulus, was used to determine 24 hours after the end of surgery The degree the After of patient satisfaction was evaluated and extubation, patients received 100 μg of fen- categorized into three levels at the 24th hour tanyl or mg of morphine every 10 when after surgery: very satisfied, satisfied, or they experienced pain at rest until they dissatisfied For patients experiencing severe reached an adequate level of comfort before PONV, 10 mg of metoclopramide or mg of starting the IV - PCA ondansetron was given intravenously Oxygen appropriate level of sedation The PCA device used a mechanical pump (B Braun, Germany) In Group F, the PCA (2 liters per minute) was administration for 24 hours postoperatively in all cases pump was programmed with the following set- Results were analysed using the Student's tings: bolus, mL; lockout time, 10 min; and t test, the Mann Whitney test and chi-square maximum dose per hours, 15 mL/h The in- tests where appropriate and values of p < 0.05 fusion solution containing 1.25 mg of fentanyl were considered statistically significant was adjusted to 50 mL by dilution with 0.9% normal saline (the concentration of fentanyl Research ethics was 25 μg/mL) In Group M, the PCA device All study procedures complied with the was programmed with the following settings: ethical principles of biomedical research bolus, mL; lockout time, 10 min; and maxi- Written informed consent was obtained from mum dose per hours, 15 mL/h The infusion patients All patient information was kept confi- solution containing 50 mg of morphine was dential and secure adjusted to 50 mL by dilution with 0.9% normal saline (the concentration of morphine was mg/mL) The background infusion dose was not applied an both groups III RESULTS A total of 90 patients were involved in this study, with 45 patients receiving morphine During the first 24 hours postoperatively, (Group M) and 45 patients receiving fentanyl non-invasive artery blood pressure, heart rate, (Group F) The demographic, surgical, and oxygen saturation, respiratory rate and occur- anesthetic characteristics of all patients by rence of untoward events were recorded at group are shown in Table There were no two hour, three hour and six hour intervals statistically significant differences between Hypotension (20% reduction in systolic blood the two groups in terms of age, sex, weight, pressure compared with preoperative base- ASA physical classification, intraoperative an- line) was treated using a vasopressor and/or esthetic sum, size of incision during surgery, IV fluid, at the anesthesiologist’s discretion If or surgical time (table 1) 90 JMR 105 E1 (7) - 2016 JOURNAL OF MEDICAL RESEARCH Table The demographic, surgical and anesthetic characteristics of the participants in each group Groups Group M (n = 45) Group F (n = 45) Age (year)ª 54.2 ± 10.3 53.7 ± 10.2 Weight (kg)ª 52.7 ± 9.8 54.6 ± 10.7 Male gender (%) 64.4 57.8 ASA I - II (%) 66.5 68.4 103.8 ± 23.7 109.2 ± 24.5 21.3 ± 4.2 22.6 ± 3.8 Intraoperative fentanyl (mcg)ª 365.2 ± 65.4 373.1 ± 59.2 Intraoperative propofol (mg)ª 556.5 ± 98.6 563 ± 102.2 Characteristics Operating time (minutes)ª Size of incision (cm)ª ª Mean value ± SD VAS at rest Group F Group M VAS at coughing * * * Group F * * * Group M * * * 2 Ext H0 H1 H2 H3 H6 H9 H12 H18 H24 Time (hour) p* 0.05) at the time the third hour on) were observed in patients of the twenty-fourth hour of measurement receiving the fentanyl IV - PCA when com- Hutchison et al (2006) found a higher rate of pared to patients receiving the morphine IV - sedation, nausea/vomiting, and pruritus in the PCA after open gastrectomy (Figure 1) These group of patients using morphine as the IV- JMR 105 E1 (7) - 2016 93 JOURNAL OF MEDICAL RESEARCH PCA in their study, as compared with the College of Anaesthetists and Faculty of Pain group using fentanyl as the IV - PCA [8] Medicine Melbourne: ANZCA & FPM Stavropoulou et al found that the rates of Macintyre, P.E (2001) Safety and nausea and pruritus were also significantly efficacy of patient-controlled analgesia Br J lower than among patients using fentanyl as Anaesth, 87(1), 36 - 46 compared to those using morphine [9] Patients on fentanyl and morphine IV- Cashman, J.N., S George (2006) Chapter 16 - Patient-Controlled Analgesia, in PCAs saw similar heart rates, blood pressure Postoperative readings, and SpO2 measurements (figure 2) Saunders: Philadelphia, 148 - 153 No cases of respiratory arrest were observed in either group These results are consistent with the previous studies comparing fentanyl to morphine [3; 9; 12] Pain Management, W.B Grass, J.A (2005) Patient-controlled analgesia Anesth Analg, 101(5), S44 - 61 Momeni, M., M Crucitti, and M De Kock (2006) Patient-controlled analgesia in the management of postoperative pain Drugs, V CONCLUSION In summary, we found that an IV - PCA using fentanyl had better analgesic efficacy, led to higher patient satisfaction, and caused fewer incidences of PONV and pruritus, compared with using a morphine IV - PCA Patients on both fentanyl and morphine IV - PCAs had normal pulmonary and cardiovascular vital signs throughout the twenty four hours that their use was monitored Acknowledgement 66(18), 2321 - 2337 Peng, P.W and A.N Sandler (1999) A review of the use of fentanyl analgesia in the management of acute pain in adults Anesthesiology, 90(2), 576 - 599 Hutchison, R (2006) A comparison of a fentanyl, morphine, patient-controlled and hydromorphone intravenous delivery for acute postoperative analgesia: a multicentered study of opioid induced adverse reactions Hospital Pharmacy, 41(7), 659 – 663 Stavropoulou, E (2008) Opioid‐ Induced Adverse Reactions of Intravenous We would like to express our sincere thanks to the doctors and medical staff at the Anesthesia and Critical Care Department in the Bach Mai Hospital for their support during this study Patient Controlled Analgesia: Comparison of Morphine and Fentanyl for Acute Postoperative Analgesia Regional Anesthesia and Pain Medicine, 33(5), e166 10 Schug SA, Palmer GM, Scott DA, REFERENCES Halliwell R, Trinca J (2015) APM:SE Working Group of the Australian and New Hurley, R.W., J.D Murphy and C Zealand College of Anaesthetists and Faculty Wu., Miller et al (2015) Acute Postoperative of Pain Medicine, Acute Pain Management: Pain, in Miller’s anesthesia R.D 2974 - 2997 Scientific Evidence (4th edition), ANZCA & Macintyre, P.E (2010) Acute Pain Ma- FPM, Melbourne, 242 nagement: Scientific Evidence 3rd ed Wor- 11 Howell, P.R (1995) Patient-controlled king Group of the Australian and New Zealand analgesia following caesarean section under 94 JMR 105 E1 (7) - 2016 JOURNAL OF MEDICAL RESEARCH general anaesthesia: a comparison of fentanyl D.A Scott (2011) Opioids, ventilation and with morphine Can J Anaesth, 42(1), 41 - 45 acute pain management Anaesth Intensive 12 Macintyre, P.E., J.A Loadsman and JMR 105 E1 (7) - 2016 Care, 39(4), 545 - 558 95 ... higher patient satisfaction, and caused fewer incidences of PONV and pruritus, compared with using a morphine IV - PCA Patients on both fentanyl and morphine IV - PCAs had normal pulmonary and cardiovascular... RESULTS A total of 90 patients were involved in this study, with 45 patients receiving morphine During the first 24 hours postoperatively, (Group M) and 45 patients receiving fentanyl non-invasive artery... group of patients using morphine as the IV- JMR 105 E1 (7) - 2016 93 JOURNAL OF MEDICAL RESEARCH PCA in their study, as compared with the College of Anaesthetists and Faculty of Pain group using fentanyl