Arzneimittelforschung 2010; 60(5): 256-261
DOI: 10.1055/s-0031-1296282
Analgesics · Anti-inflammatories · Antiphlogistics · Antirheumatic Drugs
Editio Cantor Verlag Aulendorf (Germany)

Evidence-based intravenous pain treatment with analgesic infusion regimens

Nemec Karin
1   Department of Hospital Pharmacy, Donauspital, Vienna, Austria
Cihal Petra
2   University of Vienna, Department of Pharmacology and Toxicology, Vienna, Austria
Timin Evgeny
2   University of Vienna, Department of Pharmacology and Toxicology, Vienna, Austria
Kamyar Reza Majid
2   University of Vienna, Department of Pharmacology and Toxicology, Vienna, Austria
Lemmens-Gruber Rosa
2   University of Vienna, Department of Pharmacology and Toxicology, Vienna, Austria
› Author Affiliations
Further Information

Publication History

Publication Date:
02 December 2011 (online)


Background and objective:

To survey all bedside-prepared analgesic infusions (two or more drugs within one vehicle) at a 1000-bed general hospital. To evaluate appropriate vehicles and acceptable drug combinations in analgesic infusions with regard to evidence-based therapy.


Literature review; computer simulation of pharmacokinetics with MATLAB 6.5; evaluation of pharmacokinetic or pharmacodynamic interactions and dose regimens.

Main outcome measures:

Categorisation of 19 infusion combinations used for the management of pain into acceptable and questionable combinations of components in terms of quality assurance evaluation.


Diclofenac sodium (CAS 15307-79-6), metamizole sodium (CAS 68-89-3) and tramadol hydrochloride (CAS 36282-47-0) were combined with diazepam (CAS 439-14-5), B-vitamins (CAS 67-03-8, 130-40-5, 58-56-0, 68-19-9, 98-92-0, 137-08-6), lidocaine hydrochloride (CAS 73-78-9), metoclopramide dihydrochloride (CAS 54143-57-6) and pantoprazole sodium (CAS 138786 7-1). The vehicles were Ringer, Ringer lactate, normal saline or an infusion product containing diclofenac sodium and orphenadrine citrate (CAS 4682-36-4). In 37% the vehicle used was not one recommended by the manufacturer or an incompatibility was mentioned in the product information.

The combinations of diclofenac sodium or tramadol with diazepam induce a long-lasting sedative effect by diazepam and its metabolite, but only a moderate duration of analgesia. The combination of diclofenac sodium and metamizole sodium is acceptable, although, at a lower dosage of metamizole, the duration of analgesia is shortened. No or insufficient data on therapeutic plasma levels and safe dosages has been reported for lidocaine and B-vitamins.


For all of the drug combinations in use, no interactions of clinical relevance are to be expected. In 37% of the nineteen bedside-prepared infusions, the vehicle was not suitable or incompatibilities were cited in the product information. The combinations of metamizole sodium and diclofenac sodium or tramadol in normal saline solution were in accordance with evidence-based medicine.

However, changing some infusion regimens might achieve optimisation of pain treatment with respect to duration of analgesia, and the applied number of drugs could be reduced by omitting additives with little clinical effectiveness.

  • Literature

  • 1 Pogatzki-Zahn EM, Zahn PK, Brennan TJ. Postoperative pain-clinical implications of basic research. Best Pract Res Clin Anaesthesiol. 2007; Mar 21 (1) 3-13
  • 2 Kehlet H, Jensen TS, Woolf C. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006; 367: 1618-25
  • 3 Momeni M, Crucitti M, DeKock M. Patient-controlled analgesia in the management of postoperative pain. Drugs. 2006; 66 (1) 2321-37
  • 4 Arzneistoffprofile: Basisinformation über arzneiliche Wirkstoffe. Frankfurt/Main: Govi-Verlag GmbH Pharmazeutischer Verlag; 1982-2002.
  • 5 Külpmann WR. editor. Klinisch-toxikologische Analytik Verfahren, Befunde, Interpretationen. Handbuch für Labor und Klinik. Weinheim: Wiley-Vch Verlag Gmbh 2002: 590
  • 6 Klotz U. Tramadol – the impact of its pharmacokinetic and pharmacodynamic properties on the clinical management of pain. Arzneimittelforschung. 2003; 53 (1) 681-7
  • 7 Clarot F, Goullé JP, Vaz E, Proust B. Fatal overdoses of tramadol: is benzodiazepine a risk factor of lethality?. For Sci Int. 2003; 134: 57-61
  • 8 Martindale The Complete Drug Reference. 35th ed. Sweet-man SC. editor. London: The Pharmaceutical Press 2007
  • 9 Attal N, Rouaud J, Brasseur L, Chauvin M, Bouhassira D. Systemic lidocaine in pain due to peripheral nerve injury and predictors of response. Neurology. 2004; 62: 218-25
  • 10 Drugdex®, Micromedex® Thomson Healthcare Series 2008.
  • 11 Diclobene® product information, Ratiopharm, 2007.
  • 12 Novalgin® product information, Sanofi-Aventis, 2008.
  • 13 Tramal® product information, Grünenthal, 2007.
  • 14 Tradolan® product information, Lannacher, 2007
  • 15 Gewacalm® product information, Nycomed, 2007.
  • 16 Pantoloc® product information, Nycomed, 2007.
  • 17 Hepavit® product information, Fresenius-Kabi Austria, 2006.
  • 18 Multivit B® product information, Lannacher, 1999.
  • 19 Paspertin® product information, Solvay, 2007.
  • 20 Xyloneural® product information, Gebro, 2000.
  • 21 Neodolpasse® product information, Fresenius-Kabi Austria, 2007.
  • 22 Brack A, Rittner HL, Schäfer M. Non-opioid analgesics for perioperative pain therapy. Risks and rational basis for use. Anaesthesist. 2004; 53: 263-80
  • 23 Jage J, Laufenberg-Feldmann R, Heid F. Drugs for postoperative analgesia: routine and new aspects. Part 1: nonopioids. Anaesthesist. 2008; 57: 382-90
  • 24 Stamer UM, Höthker F, Lehnen K, Stüber F. Postoperative analgesia with tramadol and metamizol Continuous infusion versus patient controlled analgesia. Anaesthesist. 2003; 52: 33-41
  • 25 Málek J, Nedelová I, Lopourová M, Stefan M, Kostál R. Diclofenac 75 mg and 30 mg orfenandrine (Neodolpasse) versus placebo and piroxicam in post-operative analgesia after arthroscopy. Acta Chir Orthop Traumatol Czech. 2004; 71: 80-3
  • 26 Aglas F, Frühwald FM, Chlud K. Results of efficacy study with diclofenac/orphenadrine infusions in patients with musculoskeletal diseases and functional disorders. Acta Med Austr. 1998; 25 (3) 86-90
  • 27 Poisindex®, Micromedex®, Thomson Healthcare Series 2008.
  • 28 Pogatzki-Zahn EM, Zahn PK. New substances and applications for postoperative pain therapy. Schmerz. 2008; 22: 353-69
  • 29 Koppert W, Ostermeier N, Sittl R, Weidner C, Schmelz M. Low dose lidocaine reduces secondary hyperalgesia by a central mode of action. Pain. 2000; 85: 217-24
  • 30 Groudine SB, Fisher HAG, Kaufman RP, Patel MK, Wilkins LJ, Mehta SA et al Intravenous lidocain speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. Anest Analg. 1998; 86: 235-9
  • 31 Herroeder S, Pecher S, Schönherr ME, Hahnenkamp K, Friess H, Böttiger BW et al Systemic lidocaine shortens length of hospital stay after colorectal surgery: a double-blinded, randomised, placebo-controlled trial. Ann Surg. 2007; 246: 192-200
  • 32 Lavand’homme P, DeKock M, Waterloos H. Intraoperative epidural analgesia combined with ketamine provides effective preventive analgesia in patients undergoing major digestive surgery. Anesthesiology. 2005; 103 (4) 813-20
  • 33 Jurna I. Analgesic and analgesia-potentiating action of B vitamins. Schmerz. 1998; 12: 136-41
  • 34 Bromm K, Herrmann WM, Schulz H. Do the B-vitamins exhibit antinociceptive efficacy in men? Results of a placebo-controlled repeated-measures double-blind study. Neuropsychobiology. 1995; 31: 156-65