Table of Contents  
Year : 2015  |  Volume : 8  |  Issue : 1  |  Page : 21-24

Preemptive parenteral paracetamol analgesia in off-pump coronary artery bypass

Department of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Submission19-Jul-2014
Date of Acceptance05-Nov-2014
Date of Web Publication25-Mar-2015

Correspondence Address:
Khaled M.A Abdelsalam
Amer Bin Thabet Street, PO Box 15215, Dammam 31444
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1687-7934.153933

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NSAIDs are routinely used for pain control in cardiac surgery; however, these drugs are burdened by side effects. Paracetamol is believed to be lacking in such side effects. The aim of this study was to examine the efficacy of preemptive intravenous paracetamol analgesia on opioid sparing in off-pump coronary artery bypass (OPCAB).
Materials and Methods
This was a prospective randomized controlled double-blinded study. A total of 80 patients scheduled for elective OPCAB were randomly allocated into two groups: in group I (the control group) 40 patients received intravenous infusion of 100 ml of normal saline solution, whereas in group II (the paracetamol study group) 40 patients received intravenous infusion of 1 g of the study drug in 100 ml solution bag. Solution bags were prepared by the pharmacy department, and treating teams were blinded to the infused solution until end of study. Hemodynamic variables and sufentanil usage were recorded and compared between the two groups.
The two groups were comparable regarding their demographic and operative data. Hemodynamic variables showed nonsignificant differences between the two studied groups. Total intraoperative consumption of sufentanil was comparable between the two groups with insignificant difference. Postoperatively, extubation time and length of ICU stay were statistically nonsignificant.
Preemptive administration of parenteral paracetamol had a limited opioid-sparing effect during intraoperative management of cardiac cases undergoing OPCAB.

Keywords: cardiac, off-pump coronary artery bypass, opioid-sparing effect, paracetamol

How to cite this article:
Abdelsalam KM. Preemptive parenteral paracetamol analgesia in off-pump coronary artery bypass. Ain-Shams J Anaesthesiol 2015;8:21-4

How to cite this URL:
Abdelsalam KM. Preemptive parenteral paracetamol analgesia in off-pump coronary artery bypass. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2021 Nov 30];8:21-4. Available from:

  Introduction Top

Analgesia is considered one of the cornerstones in perioperative anesthetic management in cardiac surgery that relies mainly on opioid analgesia with its well-known and proved drawbacks on different organ systems [1] . The introduction of parenteral NSAIDs had increased the number of patients who can benefit from nonopioid analgesics, especially those who are not to receive anything by mouth [2],[3] . In multiple clinical trials, NSAIDs have been found to be effectively reducing opioid consumption in noncardiac surgical patients [4] . However, serious side effects in cardiac surgery practice, such as tendency to increased postoperative bleeding and deterioration of renal function, had led to the conservative use of such agents as an adjuvant therapy to opioids [5] . Although not proven, acetaminophen (paracetamol), which is not a NSAID [6] , might be a safer nonopioid analgesic adjunct in cardiac surgery because it does not depress either platelet or renal functions as much as NSAIDs [7] . The aim of the present study was to assess the effectiveness of preemptive parenteral paracetamol administration as single 1 g dose on intraoperative opioid consumption and hemodynamic stability in off-pump coronary artery surgeries.

  Materials and Methods Top

This prospective randomized controlled double-blinded study was conducted at King Khaled University Hospital. After ethical committee approval, informed eligible patient consent was taken from 80 patients scheduled for elective off-pump coronary artery bypass (OPCAB). Patients were randomly allocated into one of two groups. Randomization was performed by serially numbered, sealed, opaque envelopes concealing the randomization group as determined by a computer-generated random numbers table. In group I (the control group) 40 patients received intravenous infusion of 100 ml of normal saline solution over 20 min so as to be finished 30 min before induction time. In group II (the paracetamol study group) 40 patients received intravenous infusion of 1 g of the study drug in 100 ml solution bag within same time schedule. Solution bags were prepared by the pharmacy department, and the attending anesthesiologists were blinded to the infused solution until end of study. Exclusion criteria were patients with hepatic dysfunction, sleep apnea syndrome, severe myocardial dysfunction defined as ejection fraction below 30%, morbidly obese patients, and those on long-term analgesic therapy. Anesthetic technique was standardized in both groups. Patients were premedicated with lorazepam 2 mg orally at the night of surgery and morphine 0.1 mg/kg intramuscularly 2 h preoperatively. Upon arrival to OR, oxygen was supplied to all patients through nasal cannula. ECG electrodes and pulse oximetry probe as well as bispectral index sensor were attached. Midazolam intravenous was given in increments of 1 mg to a maximum of 4 mg. A 20 G arterial catheter was inserted in the nondominant arm's radial artery under local anesthetic infiltration unless radial artery was to be harvested for grafting. Baseline readings were obtained before induction of anesthesia. Induction follows with sufentanil 1-1.5 μg/kg, midazolam 0.05-0.1 mg/kg, and rocuronium 0.9 mg/kg. After induction of anesthesia, a flow-directed, fiberoptic continuous cardiac output pulmonary artery catheter (7 F; Baxter, Irvine, California, USA) was inserted and baseline hemodynamic profile was obtained. Anesthetic maintenance was through supplemented doses of sufentanil, midazolam, rocuronium, and sevoflurane based on the discretion of the attending anesthesiologists and their interpretation of patient's clinical and hemodynamic data. Patients were mechanically ventilated with FiO 2 of 50% oxygen in air mixture and a tidal volume and respiratory rate adjusted to keep ETCO 2 between 32 and 36 mmHg.

Data collection included hemodynamic parameters including heart rate, mean arterial blood pressure, cardiac index, and systemic vascular resistance, taken at the following data points: T0=baseline, T1=postinduction, T2=skin incision, T3=90 min postinduction, T4=with chest closure at the conclusion of surgery. The T3 readings were taken in a range of timing while the heart was in normal position within the pericardial sac and not being dislocated for performing a distal anastomosis. The total intraoperative opioid consumption was calculated and registered. After surgery, all patients were transferred to the Cardiac Intensive Care Unit and controlled ventilation was continued until achieving weaning criteria where the time to extubation as well as the length of ICU stay were recorded.

Statistical analysis

Data were analyzed using a statistical software package (Graph Pad In Stat version 3.00 for Windows; Graph Pad Software Inc., San Diego, California, USA). Categorical data were expressed as numbers (%) and compared using the χ2 or Fisher's exact test as appropriate. Continuous data with a parametric distribution were presented with mean and SD and compared using an independent t-test, whereas nonparametric data were expressed as median and interquartile range and compared with the Mann-Whitney U-test. A result was deemed significant when P value was less than 0.05.

Sample size calculation

On the basis of previous unpublished data of a pilot study, we hypothesized a reduction in opioid consumption by 30% and SD of 45 with propacetamol [8] . We calculated that less than 40 patients were required in each group to give 80% power at a 5% significance level.

  Results Top

The two groups were comparable with respect to demographic and operative data [age (56.27 ± 9.18 vs. 59.31 ± 11.94 years), preoperative ejection fraction (43.65 ± 2.89 vs. 42.82 ± 3.14), operative time (229.24 ± 57.784 vs. 249.86 ± 56.06 min), and number of grafts (2.89 ± 0.85 vs. 2.96 ± 0.82) in the control group vs. the paracetamol group, respectively] ([Table 1]).
Table 1 Demographic and operative data

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Intraoperative heart rate readings were comparable among both groups. The mean arterial blood pressure as well as derived data, the cardiac index, and systemic vascular resistance showed insignificant differences between both groups at all data collection times ([Table 2]).
Table 2: Intraoperative hemodynamic variables

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Extubation time was 7.1 ± 4.54 h in the control group and 7.12 ± 5.2 h in the paracetamol group, a difference which was statistically insignificant ([Table 3]). The ICU stay was 46.55 ± 13.39 and 47.32 ± 11.36 h in the control and paracetamol groups, respectively, without significant difference ([Table 3]).
Table 3 Postoperative variables

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Sufentanil mean consumption was less in the paracetamol group (255.86 ± 54.74 µg) than in the control group (265.06 ± 54.84 µg), but this difference failed to reach statistical significance with a P value greater than 0.05 ([Figure 1]).
Figure 1: Sufentanil consumption. Data are presented as me an (SD).

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  Discussion Top

Intravenous paracetamol (Perfalgan; Bristol-Myers Squibb, Rueil-Malmaison, France) was launched on April 2004 for the short-term treatment of moderate pain in adults and for short-term treatment of fever in children and adults [9] . After years of being used widely in Europe, on November 2010, the FDA approved the use of intravenous paracetamol (OFIRMEV; Cadence Pharmaceuticals, San Diego, California, USA) in adults and children more than 2 years of age for treatment of moderate pain and fever [9] .

In this controlled double-blinded study, Paracetamol when administered preemptively showed a very limited effect regarding opioid-sparing effect during OPCAB. Preemptive principle originates from administration of analgesic drug before being subjected to noxious stimulus, altering the central processing of afferent impulses [3] . The maximum dosage of paracetamol is 1 g/6 h [9] , which was even hard to implement concerning preoperative management in OPCAB with a mean time of ~4 h. In contrast, postoperative management with second top-up dose of 1 g needs further assessment with respect to its effectiveness for postoperative pain control or opioid-sparing effect.

Paracetamol has been studied in many surgical settings such as functional endoscopic sinus surgery, cholecystectomy, hysterectomy, and orthopedic surgeries with variable favorable results [10],[11],[12],[13] . However, intravenous paracetamol analgesic properties have not been investigated in the settings of intraoperative cardiac surgery. A study in cardiac surgery patients found that absorption of acetaminophen administered via a nasogastric tube or rectally after surgery is insufficient to achieve an antipyretic plasma concentration (10 mg/ml); this was probably mainly because of delayed gastric emptying after anesthesia and surgery [14],[15] . In a study conducted by Cattabriga et al. [16] , they concluded that, in patients undergoing cardiac surgery, intravenous paracetamol in combination with tramadol provides effective pain control.

  Conclusion Top

A nonsignificant effect of preemptive paracetamol has been demonstrated during intraoperative management of OPCAB, which denotes that there is no clinical benefit from its preoperative administration. Thus, it is strongly recommended to extend analysis in further studies to evaluate postoperative adjunctive effects of paracetamol on pain control and opioid consumption after OPCAB.

  Acknowledgements Top

Conflicts of interest

No Conflict of interest.

  References Top

Munsterhjelm E, Niemi TT, Syrjälä MT, Ylikorkala O, Rosenberg PH. Propacetamol augments inhibition of platelet function by diclofenac in volunteers. Br J Anaesth 2003; 91:357-362.  Back to cited text no. 1
Lahtinen P, Kokki H, Hendolin H, Hakala T, Hynynen M. Propacetamol as adjunctive treatment for postoperative pain after cardiac surgery. Anesth Analg 2002; 95:813-819.  Back to cited text no. 2
Pettersson PH, Jakobsson J, Owall A. Intravenous acetaminophen reduced the use of opioids compared with oral administration after coronary artery bypass grafting. J Cardiothorac Vasc Anesth 2005; 19:306-309.  Back to cited text no. 3
Moote C. Efficacy of nonsteroidal anti-inflammatory drugs in the management of postoperative pain. Drugs 1992; 44:14-29.  Back to cited text no. 4
Niemi TT, Backman JT, Syrjälä MT, Viinikka LU, Rosenberg PH. Platelet dysfunction after intravenous ketorolac or propacetamol. Acta Anaesthesiol Scand 2000; 44:69-74.  Back to cited text no. 5
Sundar AS, Kodali R, Sulaiman S, Ravullapalli H, Karthekeyan R, Vakamudi M. The effects of preemptive pregabalin on attenuation of stress response to ETI and opioid sparing effect in patients undergoing OPCAB. Ann Card Anaesth 2012; 15:18-25.  Back to cited text no. 6
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Farquhar WB, Morgan AL, Zambraski EJ, Kenney WL. Effects of acetaminophen and ibuprofen on renal function in the stressed kidney. J Appl Physiol (1985) 1999; 86:598-604.  Back to cited text no. 7
Boldt J, Thaler E, Lehmann A, Papsdorf M, Isgro F. Pain management in cardiac surgery patients: comparison between standard therapy and patient-controlled analgesia regimen. J Cardiothorac Vasc Anesth 1998; 12:654-658.  Back to cited text no. 8
Schuitmaker M, Anderson BJ, Holford NH, Woollard GA. Pharmacokinetics of paracetamol in adults after cardiac surgery. Anaesth Intensive Care 1999; 27:615-622.  Back to cited text no. 9
Berger MM, Berger-Gryllaki M, Wiesel PH, Revelly JP, Hurni M, Cayeux C, et al. Intestinal absorption in patients after cardiac surgery. Crit Care Med 2000; 28:2217-2223.  Back to cited text no. 10
Koteswara CM, D S. A study on pre-emptive analgesic effect of intravenous paracetamol in functional endoscopic sinus surgeries (FESSs): a randomized, double-blinded clinical study. J Clin Diagn Res 2014; 8:108-111.  Back to cited text no. 11
Arslan M, Celep B, Ciçek R, Kalender HÜ, Yýlmaz H. Comparing the efficacy of preemptive intravenous paracetamol on the reducing effect of opioid usage in cholecystectomy. J Res Med Sci 2013; 18:172-177.  Back to cited text no. 12
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Unal C, Cakan T, Baltaci B, Baºar H. Comparison of analgesic efficacy of intravenous paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy. J Res Med Sci 2013; 18: 897-903.  Back to cited text no. 13
Jebaraj B, Maitra S, Baidya DK, Khanna P. Intravenous paracetamol reduces postoperative opioid consumption after orthopedic surgery: a systematic review of clinical trials. Pain Res Treat 2013; 2013:402510.  Back to cited text no. 14
Bannwarth B, Netter P, Lapicque F, Gillet P, Péré P, Boccard E, et al. Plasma and cerebrospinal fluid concentrations of paracetamol after a single intravenous dose of propacetamol. Br J Clin Pharmacol 1992; 34:79-81.  Back to cited text no. 15
Cattabriga I, Pacini D, Lamazza G, Talarico F, Di Bartolomeo R, Grillone G, et al. Intravenous paracetamol as adjunctive treatment for postoperative pain after cardiac surgery: a double blind randomized controlled trial. Eur J Cardiothorac Surg 2007; 32:527-531.  Back to cited text no. 16


  [Figure 1]

  [Table 1], [Table 2], [Table 3]

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