Document Type : Original Article


1 Department of Anesthesiology, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Anesthesiology, Arash Women’s Hospital, Tehran University of Medical Sciences, Tehran, Iran

3 Research Development Center, Department of Obstetrics and Gynecology, Arash Women's Hospital, Tehran University of Medical Sciences, Tehran, Iran


Background: Post-dural puncture headache (PDPH) is a common problem after spinal anesthesia. Depending on the severity of PDPH, there are both invasive and non-invasive treatments. Caffeine has been used for the treatment of PDPH since 1949, but the administration of mannitol is a novel management to tackle PDPH.This study was conducted to compare the effectiveness of acetaminophen-caffeine and mannitol in the treatment of PDPH.
Methods: We enrolled 80 patients with PDPH in the present clinical trial and observed them during 72 hours after cesarean section. Participants were randomly and equally allocated to two groups for treatment with intravenous (IV) mannitol or oral acetaminophen-caffeine. The effects of treatment were evaluated using the visual analogue scale (VAS) questionnaire at hours of 1, 2, 3, 4, 6, 12, 18, 24, and 48. SPSS software was used.
Results: Forty patients in each group completed the study. There was a significant reduction in the pain scores of the both groups after treatment, but the interaction between time and group demonstrated that mannitol administration was superior to acetaminophen-caffeine in pain reduction of the patients undergoing spinal anesthesia (P = 0.028). Patients’ satisfaction in the mannitol group was significantly higher than the caffeine group (P = 0.001).
Conclusion: This study suggests that IV mannitol infusion affects faster and earlier for the treatment of PDPH than acetaminophen-caffeine capsule. Mannitol could be probably more effective for treatment of PDPH.


  1. Doroudian MR, Norouzi M, Esmailie M, Tanhaeivash R. Dexamethasone in preventing post-dural puncture headache: A randomized, double-blind, placebo-controlled trial. Acta Anaesthesiol Belg 2011; 62(3): 143-6.
  2. Jenkinson RH. Post-dural Puncture Headache. In: Abd-Elsayed A, editor. Pain. New York, NY: Springer; 2019. p. 643-6.
  3. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004; 24 Suppl 1: 9-160.
  4. Sabharwal A, Stocks GM. Postpartum headache: Diagnosis and management. Continuing Education in Anaesthesia Critical Care and Pain 2011; 11(5): 181-5.
  5. Dabas R, Lim MJ, Sng BL. Postdural puncture headache in obstetric neuraxial anaesthesia: Current evidence and therapy. Trends in Anaesthesia and Critical Care 2019; 25: 4-11.
  6. Turnbull DK, Shepherd DB. Post-dural puncture headache: Pathogenesis, prevention and treatment. Br J Anaesth 2003; 91(5): 718-29.
  7. Dogan Erol D. The effect of oral gabapentin on postdural puncture headache. Acute Pain 2006; 8(4): 169-73.
  8. Noyan Ashraf MA, Sadeghi A, Azarbakht Z, Salehi S, Hamediseresht E. Evaluation of intravenous hydrocortisone in reducing headache after spinal anesthesia: A double blind controlled clinical study [corrected]. Middle East J Anaesthesiol 2007; 19(2): 415-22.
  9. Basurto O, X, Uriona Tuma SM, Martinez GL, Sola I, Bonfill C, X. Drug therapy for preventing post-dural puncture headache. Cochrane Database Syst Rev 2013; (2): CD001792.
  10. Stannard D. Epidural blood patching for preventing and treating postdural puncture headache. J Perianesth Nurs 2011; 26(6): 411-2.
  11. Sandesc D, Lupei MI, Sirbu C, Plavat C, Bedreag O, Vernic C. Conventional treatment or epidural blood patch for the treatment of different etiologies of post dural puncture headache. Acta Anaesthesiol Belg 2005; 56(3): 265-9.
  12. Russell R, Laxton C, Lucas DN, Niewiarowski J, Scrutton M, Stocks G. Treatment of obstetric post-dural puncture headache. Part 2: Epidural blood patch. Int J Obstet Anesth 2019; 38: 104-18.
  13. Ghaleb A. Postdural puncture headache. Anesthesiol Res Pract 2010; 2010: 102967.
  14. Sechzer PH, Abel L. Post-spinal anesthesia headache treated with caffeine. Evaluation with demand method. Part I. Curr Ther Res Clin Exp 1978; 24(3): 307-12.
  15. Ragab A, Facharzt KN. Caffeine, Is it effective for prevention of postdural puncture headache in young adult patients? Egypt J Anaesth 2014; 30(2): 181-6.
  16. Halker RB, Demaerschalk BM, Wellik KE, Wingerchuk DM, Rubin DI, Crum BA, et al. Caffeine for the prevention and treatment of postdural puncture headache: Debunking the myth. Neurologist 2007; 13(5): 323-7.
  17. Baratloo A, Rouhipour A, Forouzanfar MM, Safari S, Amiri M, Negida A. The role of caffeine in pain management: A brief literature review. Anesth Pain Med 2016; 6(3): e33193.
  18. Astorino TA, Terzi MN, Roberson DW, Burnett TR. Effect of caffeine intake on pain perception during high-intensity exercise. Int J Sport Nutr Exerc Metab 2011; 21(1): 27-32.
  19. Sawynok J. Adenosine and Pain. In: Masino S, Boison D, editors. Adenosine: A key link between metabolism and brain activity. New York, NY: Springer; 2013. p. 343-60.
  20. Sawynok J. Methylxanthines and pain. In: Fredholm BB, editor. Methylxanthines. Berlin, Heidelberg, Germany: Springer Berlin Heidelberg; 2011. p. 311-29.
  21. Rizvi MM, Singh RB, Tripathi R. New approach to treat an old problem: Mannitol for post-dural puncture headache. Indian
    J Anaesth 2016; 60(3): 229-30.
  22. Rizvi MM, Singh RB, Tripathi RK, Immaculate S. New approach to treat an old problem: Mannitol for post dural puncture headache. Indian J Anaesth 2015; 59(4): 260-1.
  23. Kassim DY, Esmat IM. Comparative study between hydrocortisone and mannitol in treatment of postdural puncture headache: A randomized double-blind study. Egypt J Anaesth 2016; 32(3): 357-63.
  24. Camann WR, Murray RS, Mushlin PS, Lambert DH. Effects of oral caffeine on postdural puncture headache. A double-blind, placebo-controlled trial. Anesth Analg 1990; 70(2): 181-4.
  25. Lin W, Geiderman J. Myth: Fluids, bed rest, and caffeine are effective in preventing and treating patients with post-lumbar puncture headache. West J Med 2002; 176(1): 69-70.
  26. Munnur U, Suresh MS. Backache, headache, and neurologic deficit after regional anesthesia. Anesthesiol Clin North Am 2003; 21(1): 71-86.
  27. Shahriari A, Sheikh M. Post-Spinal headache: A new possible pathophysiology. Anesth Pain Med 2017; 7(1): e42605.
  28. Russell R, Laxton C, Lucas DN, Niewiarowski J, Scrutton M, Stocks G. Treatment of obstetric post-dural puncture headache. Part 1: Conservative and pharmacological management. Int J Obstet Anesth 2019; 38: 93-103.
  29. Amini-Saman J, Karbasfrushan A, Ahmadi A, Bazargan-Hejazi S. Intravenous mannitol for treatment of abducens nerve paralysis after spinal anesthesia. Int J Obstet Anesth 2011; 20(3): 271-2.