Document 6477728

ANESTH ANALG 1990;701814

181

Effects of Oral Caffeine on Postdural Puncture Headache A Double-Blind, Placebo-Controlled Trial William R. Camann, Donald H. Lambert,

MD,

R. Scott Murray,

FFARACS,

Phillip s. Mushlin,

MD, PhD,

and

PhD, MD

C A M A " WR, MURRAY RS, MUSHLIN PS,

24 h later. Relief of PDPH measured as AVAS (initial VAS

LAMBERT DH. Effects of oral caffeine on postdural puncture headache. A double-blind, placebo-controlled trial. Anesth Analg 1990;70:1814.

- VAS at 4 h) was significantly better in the cafeine than in the placebo group (P = 0.014). Six patients (30%)whose PDPH was relieved by cafeine at 4 h had recurrence of symptoms the following day. Our study demonstrates that cafeine administered orally provides relief, albeit if sometimes transient, from PDPH with minimal side effects.

Forty postpartum patients with postdural puncture headache (PDPH) were randomly assigned to receive oral caffeine (300 mg) or a placebo. lntensity of headache, quantitated using a visual analogue pain scale (VAS),was assessed imniediately before drug administration and 4 and

Postdural puncture headache (PDPH) is a distressing complication of spinal anesthesia or unintentional dural puncture during attempted epidural anesthesia. Caffeine, a cerebral vasoconstrictor, has long been recognized as able to provide relief to patients with PDPH (1). Only recently has this technique enjoyed a resurgence in popularity. Intravenous caffeine, administered in combination with sodium benzoate (CSB), relieved PDPH in 85% of patients in a double-blind, placebo-controlled study (2). In another study, the combination of intravenous CSB plus hydration provided relief of PDPH in 80% of patients (3). Intravenous CSB appears to be effective in treatment of PDPH. An oral caffeine preparation, although not previously evaluated, would be more convenient and less expensive. Our study evaluated, for the first time, the efficacy of oral caffeine for treatment of PDPH in 40 postpartum patients.

Presented in part at the Society for Obstetric Anesthesia and Perinatology Annual Meeting, Seattle, Washington, May 1989. Received from the Department of Anesthesia, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Accepted for publication September 21, 1989. Address correspondence to Dr. Camann, Department of Anesthesia, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. 01990 by the International Anesthesia Research Society

Key Words: ANESTHETIC TECHNIQUES, sr1N.u-headache.

Methods The protocol was approved by our hospital's Committee for the Protection of Human Subjects from Research Risks. Written informed consent was obtained from all patients. Patients were evaluated within 1-2 days postpartum by either the primary anesthetist or a nurse-clinician, or both. When symptoms were consistent with a PDPH (frontal and/or occipital discomfort worsened by upright posture and relieved by lying supine), one of the investigators was contacted. Upon clinical diagnosis of PDPH, the patient was informed of the study protocol. Patients were excluded from the study if they had preexisting hypertension (or preeclampsia), a seizure disorder, or intolerance to caffeine, or had consumed caffeinated beverages within the previous 4 h. Study participants were requested to consume neither caffeinated beverages nor analgesics during the initial 4-h study interval. No intravenous fluids were administered, and oral intake was ad libitum. Severity of headache was scored on a 100-mm visual analogue scale (VAS) with 0 = no headache and 100 = worst headache imaginable (4). In a randomized, double-blind fashion, subjects were then given a capsule to consume by mouth. Capsules, prepared by our investigational pharmacy, contained either anhydrous caffeine powder (USP 300 mg, Spectrum Chemical Mfg. Corp., Gardena, Calif.)

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1990;70:1814

Table 1. Patient Characteristics Caffeine (n = 20)

Placebo (n = 20)

Height (an)" Weight (kg)"

29.8 & 1.4 64.1 f 0.6 72.3 f 2.6

30.6 f 1.2 64.6 f 0.6 76.5 2 2.8

NS NS NS

Parity Primiparous Mdtiparous

5 15

6 14

NS NS

Dural puncture 26 gauge 17 gauge

14 6

15 5

NS NS

Delivery Vaginal Cesarean

6 14

8

NS

12

NS

Onset of headache (postpartum) Day 1 Day 2 Day 3

8 11

12

NS NS NS

Characteristic

NS, not significant. 'Data expressed as mean

1

5 3

f SEM.

or placebo (lactose powder) and appeared identical. Headache severity (VAS) was reassessed 4 and 24 h after ingestion of the capsule. When headaches failed to resolve within 4 h, patients were encouraged to rest, to increase fluid consumption, and to take analgesics. Epidural blood patch was explained as a therapeutic option and utilized when those conservative means failed to relieve the headache. Data were expressed as mean 2 SEM. Wilcoxon rank-sum test was used to compare VAS scores between groups. ,$ analysis was used to compare frequency of blood patch. Student's t-test was used to compare demographic data. P < 0.05 was considered statistically significant.

Results Forty postpartum patients were studied; 20 received caffeine and 20 placebo. Groups did not differ in age, height, weight, parity, route of delivery (vaginal vs cesarean), size of needle involved in dural puncture (26-gauge spinal vs 17-gauge epidural), or time from dural puncture to onset of headache (Table 1). Visual analogue scale scores before administration of caffeine or placebo (To) did not differ between groups (caffeine 69 2 3; placebo 60 f 4). Improvement in VAS at 4 h (To - T4) occurred in 18 patients (90%)in the caffeine group vs 12 patients (60%)in the placebo group (Figure 1). At 4 h, VAS scores were lower in the caffeine (33 f 6) than in the placebo (49 7) group. Moreover, the magnitude of the

*

decrease in VAS was more than 300% greater in the caffeine than in the placebo group (36 f 6 vs 11 f 7; P = 0.014) (Figure 2). At 24 h, 30% of patients in the caffeine group had higher VAS scores than at 4 h. Visual analogue scale scores at 24 h did not differ between the two groups (caffeine 41 2 8; placebo 34 f 10). Fewer epidural blood patches were required in the caffeine than in the placebo group, but the difference was not statistically significant (35% vs 55%). The patches, when used, always relieved PDPH. There were no significant side effects of caffeine therapy. Two patients in the study complained of mild and transient flushing and jitteriness after receiving their capsule; one of these had received caffeine, the other placebo. When PDPHs resulting from 17-gauge dural punctures were compared with those resulting from 26gauge needles, no difference was found in initial pain scores, efficacy of caffeine, or requirement for epidural blood patches.

Discussion The present double-blind, randomized study demonstrates that a single, oral dose of caffeine (300 mg) provides relief to patients with PDPH. Beneficial effects of caffeine were rapid; relief occurred within 4 h after drug administration, and in 70% of patients, the symptoms did not recur. Side effects were infrequent and mild. The present findings are in agreement with those from studies using intravenous caffeine. Sechzer and Abel(2) demonstrated salutory effects of intravenous CSB in a randomized study in 41 patients with PDPH. A single 500-mg dose of CSB relieved the headache in 75% of patients, and a second dose, 2 h later, provided relief in an additional 10%. Thirty percent of patients had recurrence of their headache after completion of treatment. Side effects were limited to temporary dizziness and flushing. In a widely quoted, but uncontrolled nonrandomized study, Jarvis et al. (3) reported that PDPH was relieved in 80% of patients treated with intravenous CSB (500 mg) in 1L of Ringer's lactate solution, followed by an additional liter of Ringer's lactate during the subsequent 2 h. Although the results of the study by Jarvis et al. (3) were promising and consistent with those reported by Sechzer and Abel (2), this nonrandomized study is confounded by the unknown effects of acute 2-L hydration on PDPH, inasmuch as no placebo control was used. The dose of caffeine used in our study (300 mg of anhydrous powder) was 120% greater than the dose

ORAL CAFFEINE FOR POSTDURAL PUNCTURE HEADACHE

ANESTH ANALG 1990;70:1814

183

#OF PATIENTS

WORSE

8

BETTER

8

18

1 n4 Figure 1. Number of patients with improved VAS scores (T, < To)at 4 h.

a-

n4

-

'PI 0.06 vt. Placebo

*

30-

a-

10

-

lo.%&7

0-c

v

PLACEBO

I I

CAFFEINE

Figure 2 . Change in VAS pain score (To- T4).Values expressedas mean ? SEM. ' P = 0.014 vs placebo.

used in the above-mentioned intravenous studies. The CSB dose (500 mg) contains 250 mg of caffeine plus 250 mg of sodium benzoate to enhance solubility before parenteral use (5). As caffeine is almost completely absorbed after oral administration (with minimal first-pass effect) (6), our dosage was similar to that used in the aforementioned studies. Our study was limited to patients in the immediate postpartum period. During this period caffeine elimination half-life is approximately twice as long as in nonpregnant patients (12-18 h vs 6 h) owing to decreased oxidative metabolism of caffeine (7). Thus, effects of a given dose of caffeine may be more prolonged in the peripartum period than at other

times. The clinical relevance of this pharmacokinetic difference in treatment of PDPH remains to be determined. An additional concern is whether caffeine ingestion by lactating women exposes the newborn to clinically significant amounts of caffeine. Caffeine is detectable in breast milk after ingestion of either caffeinated beverages (coffee, tea, or cola) (8) or oral tablets (150-300 mg) (9). Amounts of caffeine found were quite small (0.5%-1.0%of maternal dose per liter of milk), and no caffeine was detected in the infant's urine. Only single doses of caffeine were studied and the question of accumulation after multiple doses was not addressed. Thus, although it appears safe to administer a single dose of caffeine to lactating women with PDPH, effects of multiple doses in this patient population are less clear. Caffeineis available in many beverages and overthe-counter preparations (10,ll). However, the caffeine content of a specific beverage (e.g., coffee) may vary widely (Table 2). Thus, a pharmaceutical caffeine preparation, as used in the present study, provides a more exact dosage of caffeine for treatment of PDPH. The pathogenesis of PDPH is a multistep phenomenon (12). The inciting event is a dural tear and cerebrospinal fluid leakage, which probably leads to intrathecal hypotension. Traction on the meninges and intracranial nerves could produce PDPH. However, a more appealing hypothesis, especially in view of the efficacy of vasoactive drugs on PDPH, is that intrathecal hypotension leads to dilation and distention of intracranial blood vessels (13,14). Indeed, intracranial cerebrospinal fluid pressure that is lower than lumbar cerebrospinal fluid pressure may result in painful dilation of intracranial blood vessels. This

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ANESTH ANALG 1990;70181-4

Table 2. Caffeine Content of Common Substances Substance

Caffeine content (mg)

Coffee" Freeze-dried Percolator Drip grind Tea' Black 1-min brew 5-min brew Green 1-min brew 5-min brew Cocoa' Coca-CoIab Pepsi-Cola Dr. Pepper Mountain Dew Jolt Cola Chocolate candy bar (1.2 02) No Doz' (Bristol-Myers) Vivarin' (Beecham)

66 107 142

28 47

from PDPH precludes its recommendation as a definitive treatment for this syndrome. Whether long-term relief would occur with multiple doses of caffeine in combination with fluids, analgesics, or other vasoactive drugs remains to be determined. The authors thank Linda Hertwig, RN, for referral of patients for this study, John Fanikos, RPh, and Kathleen Benfell, RPh, for preparation of the capsules, and Alyce Russo for secretarial assistance. ~~

~~

15 32 13 65 43 61 55 71 5 100 200

Data from Bunker and McWilliams (10) except Jolt Cola, from Reference 11.

"Coffee, tea, and cocoa measured as 5-02 (150 mL) cup. bCola beverages as 12-02 can. Ter tablet.

pressure differential is exaggerated in the upright position, leading to more cerebral vasodilation and worsening pain. Conversely, the pressure differential is decreased or eliminated in the supine position, lessening the stimulus for vasodilation and pain. Thus, PDPH may be explained adequately by alterations in cerebral blood flow (CBF) and spinal fluid dynamics. Caffeine may relieve PDPH because of its ability to increase cerebral vascular resistance, decrease cerebral CBF, and decrease cerebral blood volume (15-17). Recent work by Dodd et al. (18) in support of this theory has indicated the ability of intravenous caffeine to decrease global CBF in patients with PDPH. This decrease in CBF was coincident with relief of headache in all patients (n = 7). Nevertheless, the effects of caffeine on PDPH were transient, in that all seven of Dodd's patients had return of headache 48 h after caffeine, three of whom received epidural blood patches. In conclusion, this study demonstrates that a single oral dose of caffeine (300 mg) is safe and efficacious, and merits consideration in the early treatment of PDPH. In contrast to intravenous caffeine, therapy with oral caffeine is more convenient and less expensive. Although a majority of patients had relief of headaches without recurrence, some did recur after completion of treatment. The tendency for caffeine, as a single oral dose, to provide only temporary relief

References 1. Holder HG. Reactions after spinal anesthesia. JAMA 1944;124 56-7. 2. Sechzer PH, Abel L. Post-spinal anesthesia headache treated with caffeine: evaluation with demand method (part I). Curr Ther Res 1978;24307-12. 3. Jarvis AP, Greenawalt JW, Fagraeus L. Intravenous caffeine for post-dural puncture headache. Anesth Analg 1986;65:316. 4. Revill SI, Robinson JO, Rosen M, Hogg MIJ. The reliability of a linear analogue for evaluating pain. Anaesthesia 1976;31: 1191-8. 5. Rall TW.The xanthines. In: Gilman AG, Goodman LS, eds. The pharmacological basis of therapeutics. 6th ed. New York Macmillan Publishing, 1980592407. 6. Bonati M, Latini R, Galleti F, Young JF, Tognoni G, Garattini S. Caffeine disposition after oral doses. Clin Pharmacol Ther 1982;32:9aio6. 7. AIdridge A, Bailey J, Neims AH. The disposition of caffeine during and after pregnancy. Semin Perinatol 1981;5:310-4. 8. Berlin CM, Denson HM, Daniel CH, Ward RM. Disposition of dietary caffeine in milk, saliva, and plasma of lactating women. Pediatrics 1984;7359-63. 9. Tyrala EE, Dodson WE. Caffeine secretion into breast milk. Arch Dis Child 1979;54:787-800. 10. Bunker ML, McWilliams M. Caffeine content of common beverages. J Am Diet Assoc 1979;742&32. 11. The caffeine kick. US News World Rep 1988;104:76 (May 23). 12. Sechzer PH. Post spinal anesthesia headache treated with caffeine (part 11). Intracranial vascular distention, a key factor. Curr Ther Res 1979;26440-8. 13. Hattingh J, McCalden TA. Cerebrovascular effects of cerebrospinal fluid removal. S Afr Med J 1978;54:780-1. 14. Miyakawa Y, Meyer JS, Ishihara N, et al. Effect of cerebrospinal fluid removal on cerebral blood flow and metabolism in the baboon. Stroke 1977;8:34&50. 15. Moyer JH, Tashnek AB, Miller SI, Snyder H, Bowman RO, Smith CP. The effect of theophylline and caffeine on cerebral hemodynamics and cerebrospinal fluid pressure in patients with hypertensive headaches. Am J Med Sci 1952;244:377-85. 16. Denker PG. The effects of caffeine on the cerebrospinal fluid pressure. Am J Med S a 1931;181:675-80. 17. Shenkin HA, Novoack P. Clinical implications of recent studies on cerebral circulation of man. Arch Neurol Psychiatry 1954; 71:148-59. 18. Dodd JE, Efird RC, Rauck RL. Cerebral blood flow changes with caffeine therapy for postdural puncture headache (abstract). Anesthesiology 1989;71:A679.