Reviewing the literature in a sequential fashion, H.G. Holder, in a letter to the editor in JAMA in 1944, recommended the slow intravenous injection of 500 mg of caffeine sodium benzoate (CSB) for the treatment of post dural puncture headache (PDPH) [1]. He suggests that, in rare cases, a second injection may be needed after 6 hours, and states that there has never been untoward reactions associated with this therapy which had been used in "quite a number" of patients over a 15 year period.

One of the two best known articles on the treatment of PDPH with CSB, by Sechzer and Abel in 1978, reported on a group of 41 general surgical and obstetric patients with PDPH [2]. The patients were randomized to receive a 2mL injection containing either 500mg of i.v. CSB (treatment group) or normal saline (NS; control group). One to two hours later, all the patients from both groups who still had a headache were asked if they wanted a second injection. If so, they received 500mg of CSB i.v. All 41 patients were followed daily for 7 days to quantify the severity of their headache. Fifteen of the 20 (75%) patients in the treatment group had relief of their headache, while 3 patients in the control group had transient relief. Of patients who received the second injection of CSB, 2 of the 5 in the initial treatment group (CSB) obtained relief, and 10 of the 18 remaining control group patients similarly had relief of their headache. Based on this study, caffeine permanently relieved the headache of 19 of the 27 (70%) patients suffering from PDPH.

The second well-known article that has been used as the basis of many of the protocols presently used for the treatment of PDPH with CSB appeared as a letter to the editor in 1986 [3]. The authors present an unblinded, uncontrolled report of only 18 patients who were given 500 mg CSB in one liter of crystalloid, infused over one hour, followed by a second liter of i.v. fluid. If the first course of therapy was insufficient, a second course of CSB, (the same as the first) was repeated after a four-hour wait. If the second course failed to relieve the headache, the patient was offered an epidural blood patch (EBP). The authors reported that 14 of 18 (75%) of the cases were cured of their headache.

In other letters to the editor, Baumgarten [4] and Ford et al [5] extolled the simplicity of CSB therapy for PDPH, suggesting it as a first line approach to PDPH.

In 1990, Camann et al reported a double-blind, placebo controlled trial of the effects of oral caffeine in PDPH [6]. The authors randomized 40 patients to receive either a single oral dose of 300 mg anhydrous caffeine powder (equivalent to 600mg CSB) or placebo, and assessed the patients 4 and 24 hours after treatment. The initial visual analog scale (VAS) scores were similar at 4 hours, with 90% of the patients in the caffeine group vs. 60% in the placebo group showed a reduction in the VAS score. But the VAS score reduction was 3 times greater (and clinically relevant) in the caffeine group. At the 24-hour mark, 70% of the treatment group (caffeine) were still headache free. Camann et al acknowledged that there were headache recurrences in the treatment group after the completion of the study, and noted that the usefulness of multiple dose caffeine therapy needed further investigation.

In 1999, Yucel et al studied the effects of prophylactic i.v. CSB for the treatment of PDPH [7]. Sixty healthy young adult patients undergoing lower abdominal and lower extremity surgery under spinal anesthesia using a 22 gauge Quinky needle were randomized in a double-blinded, controlled study. The treatment group received 500 mg of CSB in one liter of NS, while the control group received one liter of NS, within 90 minutes of establishment of the spinal anesthetic. Their VAS scores were recorded every 4 hours for the first 48 hours. And at the end of the fifth day, the patients evaluated their overall headache complaints and were grouped into either a "none to mild headache" group or a "moderate to severe headache" group. Eleven of 30 (37%) patients in the control group, compared to 3 out of 30 (10%) in the treatment group, rated their headaches in the "moderate-severe" range. All headaches subsided within the first 5 days except for 2 patients (7%) in the control group. In addition, the overall analgesic requirements were less in the treatment group, and the VAS scores were significantly lower for the first four days in the treatment group as well, suggesting that prophylactic i.v. CSB is useful in preventing PDPH after spinal anesthesia with a 22 gauge Quinky needle.

On a more troubling note, there are at least 4 articles that cite a total of 10 patients diagnosed as having PDPH, who suffered one or more seizure on the third to sixth postpartum day [8-11]. In each case the seizures were associated with i.v. CSB therapy, with or without epidural blood patch. The CSB was given several hours prior to the seizure, but unfortunately there are no data regarding caffeine blood levels. Several of these cases may represent postpartum eclampsia, but the reports are incomplete.

Summing up, the treatment of PDPH using caffeine dates back some 60 years. The dosage and protocols commonly used are arbitrary, and there are few controlled, randomized, blinded studies in the literature. Because of this, little is known with respect to optimal dosing, timing, or frequency of this medication for the treatment of PDPH. Also, toxicity issues, especially in the obstetric population, who are at a slightly increased, but apparently significant risk of postpartum preeclampsia/eclampsia, have not been worked out. Clearly, well-designed studies examining these issues need to be carried out to provide a scientific basis for the continued use of caffeine in the treatment of PDPH. And to make matters more interesting, the effect of caffeine habituation will further confound these studies.

References

1. Holder HG. Reactions after spinal anesthesia [letter]. JAMA. 1944;124(1):56-57.
   
   
2. Sechzer PH, Abel L. Post-spinal anesthesia headache treated with caffeine. Evaluation with demand method. Part I. Curr Ther Res. 1978;24(3):307-12.
   
   
3. Jarvis AP, Greenawalt JW, Fagraeus L. Intravenous caffeine for postdural puncture headache [letter]. Anesth Analg. 1986;65(3):316-7.
   
   
4. Baumgarten RK. Should caffeine become the first-line treatment for postdural puncture headache? [letter]. Anesth Analg. 1987;66(9):913-4.
   
   
5. Ford CD, Ford DC, Koenigsberg MD. A simple treatment of post-lumbar-puncture headache. J Emerg Med. 1989;7(1):29-31.
   
   
6. 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.
   
   
7. Yucel A, Ozyalcin S, Talu GK, Yucel EC, Erdine S. Intravenous administration of caffeine sodium benzoate for postdural puncture headache. Reg Anesth Pain Med. 1999;24(1):51-4.
   
   
8. Bolton VE, Leicht CH, Scanlon TS. Postpartum seizure after epidural blood patch and intravenous caffeine sodium benzoate. Anesthesiology. 1989;70(1):146-9. Comment in: Anesthesiology. 1989;71(3):478-9.
   
   
9. Shearer VE, Cunningham G, Wallace DH, Giesecke AH. Seizures following post dural puncture headache in postpartum women. A series with suggested etiology. Anesthesiology. 1991;75(3A):A852.
   
   
10. Cohen SM, Laurito CE, Curran MJ. Grand mal seizure in a postpartum patient following intravenous infusion of caffeine sodium benzoate to treat persistent headache. J Clin Anesth. 1992;4(1):48-51.
    
    
11. Van de Velde M, Corneillie M, Vanacker B, Stevens E, Verhaeghe J, Van Assche A, Vandermeersch E. Treatment for postdural puncture headache associated with late postpartum eclampsia. Acta Anaesthesiologica Belgica. 1999;50(2):99-102.