Intraoperative Glycaemia Following Paracetamol with and without Glucose: A Randomized-Controlled Trial

DOI: 10.4236/ijcm.2013.49074   PDF   HTML     3,772 Downloads   4,915 Views  


Background: Hyperglycaemia is conversely a risk factor for perioperative complications. We are currently using a generic 3.3 g glucose containing formula of intravenous 1000 mg paracetamol for perioperative analgesia. Our main goal was to compare the trends of glycaemic values after administration of a generic 3.3 g glucose containing formula with a non-glucose containing branded formula of intravenous 1000 mg paracetamol. Methods: A exploratory proof-of-concept randomized clinical trial was conducted with 150 patients scheduled for elective gynaecologic. Patients were randomly assigned into three groups: control group (saline); active-control group: intraoperative administration of a branded non-glucose containing 1000 mg paracetamol formula; experimental group: intraoperative administration of a generic 3.3 g glucose containing 1000 mg paracetamol formula. The primary outcome was mean change from baseline in glaucoma. In case significant differences were found, the following secondary outcomes were explored: the proportion of patients with high glycaemia values (>150 mg/dL) and the proportion of patients with negative glycaemic variation. Results: Mean glycaemia change was higher after generic 3.3 g glucose containing paracetamol formula both in comparison to placebo (16.3 mg/dL [95% CI: 6.1 to 26.6]) and active-control (19.1 mg/dL [8.2 to 30.0] groups. Similar results were found in the intention-to-treat analysis. In only the experimental group, patients had high glycaemic values (11.3%). Conclusions: This study showed that in non-diabetic, under non-cardiac surgery, administration of a generic glucose-containing formula of intravenous 1000 mg paracetamol was associated with poorer glycaemic control. These results raise the question of a possible increased risk among these patients. Further studies using diabetic patients are recommended.

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R. Pereira, F. Gonçalves, J. Costa, F. Couto, C. Sá, I. Neves and L. Ormonde, "Intraoperative Glycaemia Following Paracetamol with and without Glucose: A Randomized-Controlled Trial," International Journal of Clinical Medicine, Vol. 4 No. 9, 2013, pp. 409-416. doi: 10.4236/ijcm.2013.49074.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] T. A. Raju, M. C. Torjman and M. E. Goldberg, “Perioperative Blood Glucose Monitoring in the General Surgical Population,” Journal of Diabetes Science and Technology, Vol. 3 No. 6, 2009, pp. 1282-1287.
[2] D. A. Godoy, M. Di Napoli, A. Biestro and R. Lenhardt, “Perioperative Glucose Control in Neurosurgical Patients,” Anesthesiology Research and Practice, 2013, 1-13.
[3] P. Lecomte, L. Foubert, F. Nobels, et al., “Dynamic Tight Glycemic Control During and after Cardiac Surgery Is Effective, Feasible, and Safe,” Anesthesia & Analgesia, Vol. 107, No. 1, 2008, pp. 51-58. doi:10.1213/ane.0b013e318172c557
[4] W. T. Longstreth and T. S. Inui, “High Blood Glucose Level on Hospital Admission and Poor Neurological Recovery after Cardiac Arrest,” Annals of Neurology, Vol. 15, No. 1, 1984, pp. 59-63. doi:10.1002/ana.410150111
[5] A. E. Duncan, A. Abd-Elsayed, A. Maheshwari, M. Xu, E. Soltesz and C. G. Koch, “Role of Intraoperative and Postoperative Blood Glucose Concentrations in Predicting Outcomes after Cardiac Surgery,” Anesthesiology, Vol. 112, No. 4, 2010, pp. 860-871. doi:10.1097/ALN.0b013e3181d3d4b4
[6] D. Lena, P. Kalfon, J.-C. Preiser and C. Ichai, “Glycemic Control in the Intensive Care Unit and during the Postoperative Period,” Anesthesiology, Vol. 114, No. 2, 2011, pp. 438-444. doi:10.1097/ALN.0b013e3182078843
[7] S. Akhtar, P. G. Barash and S. E. Inzucchi, “Scientific Principles and Clinical Implications of Perioperative Glucose Regulation and Control,” Anesthesia & Analgesia, Vol. 110, No. 2, 2010, pp. 478-497. doi:10.1213/ANE.0b013e3181c6be63
[8] O. Alexandre, P. Lecomte and Y. Le Manach, “Poor Intraoperative Blood Glucose Control Is Associated with a Worsened Hospital Outcome after Cardiac Surgery in Diabetic Patients,” Anesthesiology, Vol. 103, No. 4, 2010, pp. 687-694.
[9] G. V. Bochicchio, L. Salzano, M. Joshi, K. Bochicchio and T. M. Scalea, “Admission Preoperative Glucose Is Predictive of Morbidity and Mortality in Trauma Patients Who Require Immediate Operative Intervention,” The American Journal of Surgery, Vol. 71, No. 2, 2005, pp. 171-174.
[10] G. V. Bochicchio, J. Sung, M. Joshi, et al., “Persistent Hyperglycemia Is Predictive of Outcome in Critically Ill Trauma Patients,” Journal of Trauma, Vol. 58, No. 5, 2005, pp. 921-924. doi:10.1097/01.TA.0000162141.26392.07
[11] S. Ganai, M. K. F. Lee, et al., “Adverse Outcomes of Geriatric Patients Undergoing Abdominal Surgery Who Are at High Risk for Delirium,” Archives of Surgery, Vol. 142, No. 11, 2007, pp. 1072-1078. doi:10.1001/archsurg.142.11.1072
[12] G. E. Umpierrez, S. D. Isaacs, N. Bazargan, X. You, L. M. Thaler and A. E. Kitabchi, “Hyperglycemia: An Independent Marker of In-Hospital Mortality in Patients with Undiagnosed Diabetes,” The Journal of Clinical Endocrinology & Metabolism, Vol. 87, No. 3, 2002, pp. 978-982. doi:10.1210/jc.87.3.978
[13] E. P. Krenzelok and M. A. Royal, “Confusion: Acetaminophen Dosing Changes Based on NO Evidence in Adults,” Drugs in R&D, Vol. 12, No. 2, 2012, pp. 45-48
[14] K. Toussaint, X. C. Yang, M. A. Zielinski, et al., “What Do We (Not) Know about How Paracetamol (Acetaminophen) Works?” Journal of Clinical Pharmacy and Therapeutics, Vol. 35, No. 6, 2010, pp. 617-638. doi:10.1111/j.1365-2710.2009.01143.x
[15] H. F. Miranda, M. M. Puig, J. C. Prieto and G. Pinardi, “Synergism between Paracetamol and Nonsteroidal Anti-Inflammatory Drugs in Experimental Acute Pain,” Pain, Vol. 121, No. 1, 2006, pp. 22-28. doi:10.1016/j.pain.2005.11.012
[16] S. E. Siegelaar, J. Hermanides, H. M. Oudemans-van Straaten, et al., “Mean Glucose during ICU Admission Is Related to Mortality by a U-Shaped Curve in Surgical and Medical Patients: A Retrospective Cohort Study,” Critical Care, Vol. 14, No. 6, 2010, p. R224. doi:10.1186/cc9369
[17] G. E. Umpierrez, D. Smiley, A. Zisman, et al., “Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients with Type 2 Diabetes (RA BBIT 2 Trial),” Diabetes Care, Vol. 30, No. 9, 2007, pp. 2181-2186. doi:10.2337/dc07-0295
[18] R. Hirose, F. Xu, K. Dang, et al., “Transient Hyperglycemia Affects the Extent of Ischemia-Reperfusion-Induced Renal Injury in Rats,” Anesthesiology, Vol. 108, No. 3, 2008, pp. 402-414. doi:10.1097/ALN.0b013e318164cff8
[19] A. M. Sheehy and R. A. Gabbay, “An Overview of Preoperative Glucose Evaluation, Management, and Perioperative Impact,” Journal of Diabetes Science and Technology, Vol. 3, No. 6, 2009, pp. 1261-1269.
[20] L. F. Meneghini, “Perioperative Management of Diabetes: Translating Evidence into Practice,” Cleveland Clinic Journal of Medicine, Vol. 76, No. 4, 2009, pp. S53-S59. doi:10.3949/ccjm.76.s4.09
[21] A. Gautnam, A. Balusch, A. D. Kaye and E. A. Frost, “Modern Strategies for the Anesthesic Management of the Patient with Diabetes,” M.E.J. Anesthesia, Vol. 20, No. 2, 2009, pp. 187-197.
[22] G. Van Den Berghe, P. Wouters, F. Weekers and C. Verwaest, “Intensive Insulin Therapy in Critically Ill Patients,” The New England Journal of Medicine, Vol. 345, No. 19, 2001, pp. 1356-1367.
[23] S. Finfer, FRCP, FJFICM, et al., “Intensive versus Conventional Glucose Control in Critically Ill Patients,” The New England Journal of Medicine, Vol. 360, No. 13, 2009, pp. 1283-1297. doi:10.1056/NEJMoa0810625
[24] E. S. Moghissi, M. T. Korytkowski, M. Di Nardo, et al., “American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control,” Diabetes Care, Vol. 32, No. 6, 2009, pp. 1119-1131. doi:10.2337/dc09-9029
[25] J. Steven and S. Nicolson, “Perioperative Management of Blood Glucose during Open Heart Surgery in Infants and Children,” Pediatric Anesthesia, Vol. 21, No. 5, 2011, pp. 530-537. doi:10.1111/j.1460-9592.2011.03587.x
[26] G. Y. Gandhi, G. A. Nuttall, M. D. Abel, et al., “Intraoperative Hyperglycemia and Perioperative Outcomes in Cardiac Surgery Patients,” Mayo Clinic Proceedings, Vol. 80, No. 7, 2005, pp. 862-866. doi:10.4065/80.7.862
[27] F. Puskas, H. P. Grocott, W. D. White, J. P. Mathew, M. F. Newman and S. Bar-Yosef, “Intraoperative Hyperglycemia and Cognitive Decline after CABG,” The Annals of Thoracic Surgery, Vol. 84, No. 5, 2007, pp. 1467-1473. doi:10.1016/j.athoracsur.2007.06.023
[28] F. Bilotta and G. Rosa, “Glucose Management in the Neurosurgical Patient: Are We yet Any Closer?” Current Opinion in Anaesthesiology, Vol. 23, No. 5, 2010, pp. 539-543. doi:10.1097/ACO.0b013e32833e150a
[29] L. S. Kao, D. Meeks, V. A. Moyer and K. P. Lally “PeriOperative Glycaemia Control Regimens for Preventing Surgical Site Infection in Adults,” Cochrane Database of Systematic Reviews, John Wiley & Sons, Ltd, New York, p. 12.
[30] M. Ramos, Z. Khalpey, S. Lipsitz, et al., “Relationship of Perioperative Hyperglycemia and Postoperative Infections in Patients Who Undergo General and Vascular Surgery,” Transactions of the Meeting of the American Surgical Association, Vol. 126, 2008, pp. 228-234. doi:10.1097/SLA.0b013e31818990d1
[31] A. K. M. Lipshutz and M. A. Gropper, “Perioperative Glycemic Control: An Evidence-Based Review,” Anes-thesiology, Vol. 110, No. 2, 2009, pp. 408-421.
[32] G. P. Joshi, F. Chung, M. A. Vann, et al., “Society for Ambulatory Anesthesia Consensus Statement on Perioperative Blood Glucose Management in Diabetic Patients Undergoing Ambulatory Surgery,” Anesthesia & Analgesia, Vol. 111, No. 6, 2010, pp. 1378-1387. doi:10.1213/ANE.0b013e3181f9c288
[33] D. Kansagara, R. Fu, M. Freeman, F. Wolf and M. Helfand, “Intensive Insulin Therapy in Hospitalized Patients: A Systematic Review,” Annals of Internal Medicine, Vol. 154, No. 4, 2011, pp. 268-282. doi:10.7326/0003-4819-154-4-201102150-00008
[34] C. Ryan, A. Vega and A. Drash, “Cognitive Deficits in Adolescents Who Developed Diabetes Early in Life,” Pediatrics, Vol. 75, No. 5, 1985, pp. 921-927.
[35] P. E. Cryer, L. Axelrod, A. B. Grossman, S. R. Heller, V. M. Montori, E. R. Seaquist and F. J. Service “Evaluation and Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical Practice Guidelines,” The Journal of Clinical Endocrinology & Metabolism, Vol. 94, 2009, pp. 709-728.
[36] C. H. Jensen, P. Berthelsen, C. Kühl and H. Kehlet, “Effect of Epidural Analgesia on Glucose Tolerance during Surgery,” Acta Anaesthesiologica Scandinavica, Vol. 24, No. 6, 1908, pp. 472-474. doi:10.1111/j.1399-6576.1980.tb01586.x
[37] N. K. Skjaervold, E. Solligard, D. R. Hjelme and P. Aadahl, “Continuous Measurement of Blood Glucose: Validation of a New Intravascular Sensor,” Anesthesiology, Vol. 114, No. 1, 2011, pp. 120-125. doi:10.1097/ALN.0b013e3181ff4187
[38] H. F. Pidcoke, C. E. Wade, E. A. Mann, et al., “Anemia Causes Hypoglycemia in Intensive Care Unit Patients Due to Error in Single-Channel Glucometers: Methods of Reducing Patient Risk,” Critical Care Medicine, Vol. 38, No. 2, 2010, pp. 471-476. doi:10.1097/CCM.0b013e3181bc826f
[39] E. A. Mann, J. Salinas, H. F. Pidcoke, S. E. Wolf, J. B. Holcomb and C. E. Wade, “Error Rates Resulting from Anemia Can Be Corrected in Multiple Commonly Used Point-of-Care Glucometers,” Journal of Trauma, Vol. 64, No. 1, 2008, pp. 15-20.
[40] M. J. Rice, A. D. Pitkin and D. B. Coursin, “Glucose Measurement in the Operating Room: More Complicated than It Seems,” Anesthesia & Analgesia, Vol. 110, No. 1, 2010, pp. 1058-1065.
[41] F. Akinbami, S. Segal, J. L. Schnipper, M. Stopfkuchen-Evans, J. Mills and S. O. Rogers, “Tale of Two Sites: Capillary versus Arterial Blood Glucose Testing in the Operating Room,” AJS, Vol. 203, No. 4, 2012, pp. 423-427.
[42] J. L. Schnipper, M. Magee, K. Larsen, S. E. Inzucchi and G. Maynard, “Society of Hospital Medicine Glycemic Control Task Force Summary: Practical Recommendations for Assessing the Impact of Glycemic Control Efforts,” Journal of Hospital Medicine, Vol. 3, No. S5, 2008, pp. 66-75. doi:10.1002/jhm.356

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