Gender is believed to be an independent risk factor for the development of post-dural puncture headache, but there are some of the inconsistencies in the available data. This systematic review examined a total of 18 trials (2,163 males, 1,917 females). The odds of developing a post-dural puncture headache were significantly lower for male than nonpregnant female subjects (odds ratio = 0.55; 95% confidence interval, 0.44-0.67). Although the authors found that nonpregnant female subjects seem to have a higher incidence of post-dural puncture headache than males, the etiology behind these findings is not clear from the current meta-analysis.

GENDER is believed to be an independent risk factor for the development of post–dural puncture headache (PDPH). Females are generally believed to have a higher incidence of PDPH; however, previous data1may not have adjusted for parturients (22% incidence of PDPH1) who may have received relatively more lumbar punctures than similarly aged males and, as a result, may have skewed previous data examining the overall incidence of PDPH (i.e. , 7% for males vs.  14% for females overall1). Some data in the anesthesiology literature suggest that there may be no significant difference in the incidence of PDPH between males and females.2–4For example, a multivariate analysis of 1,021 spinal anesthetics noted that gender was not a significant predictor of PDPH (P = 0.12). However, other randomized data indicate that females may have a higher incidence of PDPH compared with males (7.4% for females vs.  3.4% for males).5 

There may be several reasons why females may have a higher incidence of PDPH. It is well recognized that females have a higher incidence of certain types of headaches, such as tension type and migraine.6,7In addition, there may be differences in the processing of nociceptive information such that females may exhibit greater sensitivity to experimentally induced pain and demonstrate greater temporal summation of mechanically evoked pain.8–10Finally, some data also suggest that sex hormones may influence the incidence of certain types of headaches,11,12but other data suggests that hormonal levels may not influence the incidence of PDPH.13Because of some of the inconsistencies in the available data, we performed a meta-analysis of randomized trials to determine the extent of gender (excluding parturients) as a risk factor for the development of PDPH.

The National Library of Medicine’s PubMed database was searched for the time period 1966 to August 31, 2004. PubMed was searched for all articles containing text words postdural puncture headache  (13,866 articles), spinal headache  (13,823 articles), and headache  (33,467 articles), which yielded a total of 33,467 articles. A second search was performed using the text words epidural anesthesia  (10,255 articles), spinal anesthesia  (7,639 articles), lumbar puncture  (5,097 articles), myelogram  (7,487 articles), and spinal  (193,389 articles), which yielded a total of 205,145 articles. These two searches were combined using the Boolean term AND  (3,025 articles). This search was limited to the English language (2,213 articles) and then to human subjects, which resulted in 306 abstracts. The full article of each abstract was then reviewed by one of the authors for inclusion into the meta-analysis. No minimum sample sizes were invoked for inclusion of studies in the analysis. Any disputes were resolved by agreement of at least two reviewers.

For the purposes of this meta-analysis, PDPH was defined a headache occurring after a single lumbar puncture that was postural in nature. To be included in this meta-analysis, the postural component of PDPH needed to be clearly indicated in the article. Other inclusion criteria included trials that were randomized, that evaluated only adult patients, and where the incidence of PDPH studied and the data were available for both genders. Exclusion criteria included articles where definition of PDPH was unclear (i.e. , did not indicate a postural component of the headache), only one gender was studied (e.g. , parturients), the separate incidence of PDPH for male and nonpregnant female subjects was not available, or randomization of subjects was not performed. We excluded any studies that examined parturients because the physiologic changes in pregnancy may potentially influence how pain (including headache) is perceived, and the main focus of our meta-analysis was on a comparison of PDPH between nonpregnant females and males. Our meta-analysis also excluded articles investigating the incidence of PDPH after a continuous spinal catheter.

Data (e.g. , study characteristics, type and size of lumbar puncture needle, number and mean age of males and nonpregnant female subjects, incidence of PDPH) were collected from each article, and results were recorded. Data were extrapolated from figures or tables as needed; however, an attempt was made to contact the original authors before extrapolation. All reported data were included as unique observations and subgrouped as described below. PDPH data were weighted by sample size. The overall incidence of PDPH (weighted for patient observations) after lumbar puncture between male and nonpregnant female subjects were compared. The data for incidence of PDPH was subdivided by needle type (e.g. , cutting vs.  pencil point), needle size, and age.

The level of significance for all tests was set at an α level of 0.05. Demographic data were compared with chi-square (needle size and shape) and t  tests (age). A fixed effects model was used. All statistical analyses (i.e. , determination of the pooled estimate, test for heterogeneity) were performed with RevMan 4.2.7 (The Cochrane Collaboration, 2004) and SPSS 10.0.7 (SPSS Inc., Chicago, IL). After the data compilation was complete, we performed further analyses to assess the validity of our conclusions. We performed an analysis of the file drawer problem (i.e. , how many unpublished studies or subjects showing no difference between treatment regimens would be needed to be “discovered” in someone’s file drawer to invalidate our results) as described by Rosenthal.14 

Our search resulted in 306 abstracts of which a total of 18 articles5,15–32met all inclusion criteria. There were 2,163 male subjects and 1,917 nonpregnant female subjects in the 18 randomized trials used for the meta-analysis. A total of 288 articles were rejected for the following reasons: 113 did not include an adequate definition of PDPH (i.e. , did not indicate a postural component of the headache), 68 assessed only one gender, 34 did not provide breakdown data for incidence of PDPH for male and female subjects, 35 were not randomized, and 38 were pediatric studies.

Table 1provides a detailed overview of studies included in the analysis. Table 2shows the characteristics of the studies used for the meta-analysis. The majority of studies were from Europe (13 trials) and only performed their study in one center (16 trials). Table 3shows the demographic and study data arranged by gender. There were more male (2,163 or 53%) than nonpregnant female (1,917 or 47%) subjects. Nonpregnant female subjects overall were significantly older (42.5 ± 7.0 vs.  38.8 ± 9.8 yr, mean ± SD; P < 0.001) than male subjects. There were no significant differences in the percentages of pencil-point spinal needles or size of spinal needles between the two groups. Table 4shows the adjusted incidence of PDPH stratified by needle size and shape. We were not able to provide a meaningful weighted incidence stratified by age because of the paucity of data (i.e. , not all trials provided breakdown of age by gender).

Table 1. Overview of Studies 

Table 1. Overview of Studies 
Table 1. Overview of Studies 

Table 2. Study Characteristics 

Table 2. Study Characteristics 
Table 2. Study Characteristics 

Table 3. Demographic Data 

Table 3. Demographic Data 
Table 3. Demographic Data 

Table 4. Adjusted Incidence of PDPH for Different Needle Factors 

Table 4. Adjusted Incidence of PDPH for Different Needle Factors 
Table 4. Adjusted Incidence of PDPH for Different Needle Factors 

Figure 1shows the pooled estimate of all included studies. The variation in results across studies (i.e. , heterogeneity) was not statistically significant (I2= 22.0, P = 0.19). The odds ratio of a male subject developing a PDPH versus  a nonpregnant female subject was 0.55 (95% confidence interval, 0.44–0.67), i.e. , male subjects have approximately one half of the odds of developing PDPH compared with nonpregnant female subjects (or the odds of developing a PDPH are approximately 2 times greater in female than in male subjects). A file drawer analysis of our data revealed that 1,731 subjects showing no difference in the incidence of PDPH between male and nonpregnant female subjects would be needed to nullify our results.

Fig. 1. This figure shows the weighted (pooled) estimate for the incidence of post–dural puncture headache. n represents the actual number of post–dural puncture headaches, and N represents the actual number of male of female subjects. The entire diamond (pooled estimate) lies to the left of the odds ratio (OR) = 1 (which represents no difference), suggesting that male gender is associated with a significant lower odds (odds ratio = 0.55; confidence interval [CI], 0.44–0.67) of post–dural puncture headache than that for females. 

Fig. 1. This figure shows the weighted (pooled) estimate for the incidence of post–dural puncture headache. n represents the actual number of post–dural puncture headaches, and N represents the actual number of male of female subjects. The entire diamond (pooled estimate) lies to the left of the odds ratio (OR) = 1 (which represents no difference), suggesting that male gender is associated with a significant lower odds (odds ratio = 0.55; confidence interval [CI], 0.44–0.67) of post–dural puncture headache than that for females. 

Close modal

The extent of gender as an independent risk factor for the development of PDPH is not clear.33We performed a meta-analysis of available randomized trials to determine the effect of gender on the incidence of PDPH and found that nonpregnant female subjects had significantly higher odds of developing PDPH than male subjects. This finding occurred despite the fact that nonpregnant female subjects overall were significantly older, which would theoretically favor a lower incidence of PDPH in female subjects.3,26There were no significant differences between the two groups in other factors (i.e. , type of spinal needle or needle size) that might have influenced the incidence of PDPH.34 

Although it is not apparent why nonpregnant females would have a higher incidence of PDPH, there may be several physiologic, anatomical, or psychosocial possibilities to explain the higher reported incidence of PDPH in nonpregnant females. Female subjects seem to process nociceptive information differently than male subjects. Although this topic is complex, it seems that female subjects generally exhibit greater sensitivity to experimental noxious stimuli than males.10,35,36Females also have higher temporal summation of mechanically evoked pain, indicating that females may demonstrate a greater degree of central sensitization compared with males.9Gender differences in patterns of cerebral activation in response to noxious stimuli are also noted, with females having greater activation of the contralateral prefrontal cortex, an activation pattern associated with increased pain perception.8,37In addition to gender differences in nociceptive thresholds and processing, there may be psychosocial factors that may contribute to some of the differences seen in experimentally induced pain.38Socially learned, gender role expectations of pain may influence the incidence of reported pain because male subjects are less likely to disclose the presence of pain than female subjects, and these psychosocial variables may contribute to a significant portion of the differences seen.38,39Postoperatively, females report a higher incidence of headache and pain despite possibly having a greater analgesic response to opioids than men.40–42Therefore, both biologic and psychosocial factors may contribute to the differences in pain perception, which may in part explain the increased incidence of reported PDPH in female subjects in our study.

There are other reasons why females might hypothetically report a higher incidence of PDPH. Vasodilation of the cerebral vessels normally occurs in patients with PDPH as a homeostatic mechanism to compensate for cerebrospinal fluid loss and may theoretically contribute to the severity of PDPH.43–46Gender differences in the cerebral vasodilatory response are present with premenopausal females exhibiting significantly greater vasodilatory response to acetazolamide than males or postmenopausal females.47,48In addition, the incidence of PDPH seems to increase in females relative to male subjects after onset of puberty.49Estrogen has been shown to mediate cerebral artery tone and may dilate cerebral pial vessels.50,51Finally, younger (aged 30–40 yr), presumably premenopausal women have a significantly higher cerebrovascular reactivity compared with older women (aged 50–60 yr) and men.52 

There are several limitations to our study. We were unable to obtain all of the possible data for our meta-analysis because it is possible that not all relevant articles were obtained from our current literature strategy, some of the authors did not respond to our requests, and we were unable to extract the relevant data (i.e. , incidence of PDPH for male vs.  nonpregnant female) for some studies; however, the file drawer analysis suggests that a relatively large number of subjects (approximately 1,700) showing no difference in the incidence of PDPH between male and nonpregnant female subjects would be needed to nullify our results. Although gender cannot be randomized, we limited our meta-analysis to randomized controlled trials because data from observational (nonrandomized) trials may not be of equivalent quality (e.g. , less stringent or incomplete data collection than randomized trials, lack of blinding, presence of possible bias or confounding), and combining randomized and nonrandomized data into a single pooled estimate (which is extremely controversial) may distort the results through the introduction of bias and confounding. The trials obtained from our literature search that did not meet our inclusion criteria for further statistical analysis contained 1,908 males, 1,914 nonpregnant females, and 9,566 parturients. The overall incidences of PDPH for this and previous1observational data are 6.67% (398 in 5,971) for males and 8.58% (527 in 6,140) for nonpregnant females (unadjusted relative risk of male/female = 0.78; P < 0.0001). Although this does corroborate our data (i.e. , lower risk for PDPH in males), it is possible that additional analyses and adjustment of observational data may result in different findings than our own. In addition, there may be other observational data not identified by our literature search, which may also provide different results from our data.

Our results may not be generalizable to other populations (which were part of our exclusion criteria) such as parturients or pediatric subjects. Because we excluded studies examining parturients from meta-analysis, we are unable to determine whether parturients may also have a higher relative risk for PDPH versus  males. We also did not weight by the quality scoring of the randomized controlled trials used or assess the articles in a blinded fashion because the effects of these interventions on the results of meta-analysis are uncertain.53–56There are also limitations of the meta-analytic technique per se . Discrepancies between meta-analyses and subsequently performed large, randomized controlled trials have been reported, although the reasons for this are controversial.57–59There also may be is may be the presence of publication bias because studies that have positive findings are published more frequently in English-language (rather than non–English-language) journals60,61; however, the effect of excluding non-English trials on the results of a meta-analysis is uncertain, and the inclusion of these trials may actually result in a more conservative estimate of the treatment effect in some cases.62 

In summary, our systematic review indicates that female (nonpregnant) gender may be a risk factor for the development of PDPH. Nonpregnant females have approximately twice the odds of developing a PDPH compared with males. Our analysis does not allow us to determine the rationale behind these findings, although several mechanisms may contribute to females having a higher incidence of PDPH. The development of PDPH is a potentially debilitating complication of neuraxial anesthesia, and these techniques should not be withheld from female patients because there are many other potential benefits63–66of neuraxial anesthesia and analgesia; however, clinicians consider this higher incidence of PDPH as they weigh the potential risks and benefits of the procedure in females. Nevertheless, clinicians performing lumbar punctures/spinal anesthetics generally should consider implementing available techniques (e.g. , use of pencil-point rather than cutting needles, use of smaller-gauge needles, insertion of a beveled needle in a “parallel” rather than “perpendicular” orientation with respect to the dural fibers) to decrease the incidence of PDPH in both genders.

The authors thank Marguerite Littleton-Kearney, D.N.Sc., R.N., F.A.A.N. (Associate Professor, Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University; Baltimore, Maryland), for her input. They also thank the following colleagues for taking the time out of their busy schedules to review and retrieve their original data for incorporation in this meta-analysis: Jose De Andrés, M.D., Ph.D. (Professor of Anesthesia, Department of Anesthesiology and Critical Care, Valencia University General Hospital, Valencia, Spain), Sinan Karaoglu, M.D. (Associate Professor, Department of Orthopedics and Traumatology, Erciyes University, Kayseri, Turkey), Per Rosenberg, M.D., Ph.D. (Professor, Department of Anesthesiology and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland), Michael Strupp, M.D. (Professor of Neurology, University of Munich, Munich, Germany), Trey Sunderland, M.D. (Chief, Geriatric Psychiatry Branch, National Institutes of Mental Health, Bethesda, Maryland), and Aysen Yucel, M.D. (Professor, Department of Algology, Istanbul University; Istanbul, Turkey).

Vandam LD, Dripps RD: Long-term follow-up of patients who received 10,098 spinal anesthetics. JAMA 1956; 161:586–91
Dittmann M, Schaeffer HG, Renke F, Greve I: Spinal anaesthesia with 29 gauge Quincke point needles and post dural puncture headache in 2,378 patients. Acta Anaesthesiol Scand 1994; 38:691–3
Lybecker H, Moller JT, May O, Nielsen HK: Incidence and prediction of postdural puncture headache: A prospective study of 1021 spinal anesthesias. Anesth Analg 1990; 70:389–94
Takkila PJ, Heine H, Tervo RR: Comparison of Sprotte and Quincke needles with respect to postdural puncture headache and backache. Reg Anesth 1992; 17:283–7
Kang SB, Goodnough DE, Lee YK, Olson RA, Borshoff JA, Furlano MM, Krueger LS: Comparison of 26- and 27-G needles for spinal anesthesia for ambulatory surgery patients. Anesthesiology 1992; 76:734–8
Schwartz BS, Stewart WF, Simon D, Lipton RB: Epidemiology of tension-type headache. JAMA 1998; 279:381–3
Silberstein SD: Headache and female hormones: What you need to know. Curr Opin Neurol 2001; 14:323–33
Paulson PE, Minoshima S, Morrow TJ, Casey KL: Gender differences in pain perception and patterns of cerebral activation during noxious heat stimulation in humans. Pain 1998; 76:223–9
Sarlani E, Greenspan JD: Gender differences in temporal summation of mechanically evoked pain. Pain 2002; 97:163–9
Sarlani E, Farooq N, Greenspan JD: Gender and laterality differences in thermosensation throughout the perceptible range. Pain 2003; 106:9–18
Silberstein SD, Merriam GR: Physiology of the menstrual cycle. Cephalalgia 2000; 20:148–54
MacGregor EA, Hackshaw A: Prevalence of migraine on each day of the natural menstrual cycle. Neurology 2004; 63:351–3
Echevarria M, Caba F, Rodriguez R: The influence of the menstrual cycle in postdural puncture headache. Reg Anesth Pain Med 1998; 23:485–90
Rosenthal R: Meta-analysis: A review. Psychosom Med 1991; 53:247–71
Corbey MP, Bach AB, Lech K, Frorup AM: Grading of severity of postdural puncture headache after 27-gauge Quincke and Whitacre needles. Acta Anaesthesiol Scand 1997; 41:779–84
Dahl JB, Schultz P, Anker-Moller E, Christensen EF, Staunstrup HG, Carlsson P: Spinal anaesthesia in young patients using a 29-gauge needle: Technical considerations and an evaluation of postoperative complaints compared with general anaesthesia. Br J Anaesth 1990; 64:178–82
De Andres J, Valia JC, Errando C, Rico G, Lopez-Alarcon MD: Subarachnoid anesthesia in young patients: A comparative analysis of two needle bevels. Reg Anesth Pain Med 1999; 24:547–52
Despond O, Meuret P, Hemmings G: Postdural puncture headache after spinal anaesthesia in young orthopaedic outpatients using 27-g needles. Can J Anaesth 1998; 45:1106–9
Esmaoglu A, Karaoglu S, Mizrak A, Boyaci A: Bilateral versus  unilateral spinal anesthesia for outpatient knee arthroscopies. Knee Surg Sports Traumatol Arthrosc 2004; 12:155–8
Hilton-Jones D, Harrad RA, Gill MW, Warlow CP: Failure of postural manoeuvres to prevent lumbar puncture headache. J Neurol Neurosurg Psychiatry 1982; 45:743–6
Kang SB, Goodnough DE, Lee YK, Olson RA, Borshoff JA, Furlano MM, Krueger LS: Comparison of 26- and 27-G needles for spinal anesthesia for ambulatory surgery patients. Anesthesiology 1992; 76:734–8
Linker G, Mirza N, Manetti G, Meyer M, Putnam KT, Sunderland T: Fine-needle, negative-pressure lumbar puncture: A safe technique for collecting CSF. Neurology 2002; 59:2008–9
Murata Y, Yamagata M, Ogata S, Shimizu K, Ikeda Y, Hirayama J, Yamada H: The influence of early ambulation and other factors on headache after lumbar myelography. J Bone Joint Surg Br 2003; 85:531–4
Pippa P, Barbagli R, Rabassini M, Doni L, Rucci FS: Postspinal headache in Taylor’s approach: A comparison between 21- and 25-gauge needles in orthopaedic patients. Anaesth Intensive Care 1995; 23:560–3
Puolakka R, Haasio J, Rosenberg PH, Tuominen M: Comparison of double-hole and single-hole pencil-point needles for spinal anesthesia with hyperbaric bupivacaine. Reg Anesth Pain Med 1998; 23:271–7
Rasmussen BS, Blom L, Hansen P, Mikkelsen SS: Postspinal headache in young and elderly patients: Two randomised, double-blind studies that compare 20- and 25-gauge needles. Anaesthesia 1989; 44:571–3
Santanen U, Rautoma P, Luurila H, Erkola O, Pere P: Comparison of 27-gauge (0.41-mm) Whitacre and Quincke spinal needles with respect to post-dural puncture headache and non-dural puncture headache. Acta Anaesthesiol Scand 2004; 48:474–9
Sengupta P, Bagley G, Lim M: Prevention of postdural puncture headache after spinal anaesthesia for extracorporeal shockwave lithotripsy: An assessment of prophylactic epidural blood patching. Anaesthesia 1989; 44:54–6
Strupp M, Brandt T: Should one reinsert the stylet during lumbar puncture? (letter). N Engl J Med 1997; 336:1190
Strupp M, Schueler O, Straube A, Von Stuckrad-Barre S, Brandt T: “Atraumatic” Sprotte needle reduces the incidence of post-lumbar puncture headaches. Neurology 2001; 57:2310–2
Tourtellotte WW, Henderson WG, Tucker RP, Gilland O, Walker JE, Kokman E: A randomized, double-blind clinical trial comparing the 22 versus  26 gauge needle in the production of the post-lumbar puncture syndrome in normal individuals. Headache 1972; 12:73–8
Vilming ST, Schrader H, Monstad I: Post-lumbar-puncture headache: the significance of body posture: A controlled study of 300 patients. Cephalalgia 1988; 8:75–8
Drasner K, Swisher JL: Delayed complications and side effects of regional anesthesia, Regional Anesthesia and Analgesia. Edited by Brown DL. Philadelphia, WB Saunders, 1996, pp 462–76Brown DL
WB Saunders
Halpern S, Preston R: Postdural puncture headache and spinal needle design: Metaanalyses. Anesthesiology 1994; 81:1376–83
Fillingim RB, Maixner W, Kincaid S, Silva S: Sex differences in temporal summation but not sensory-discriminative processing of thermal pain. Pain 1998; 75:121–7
Chesterton LS, Barlas P, Foster NE, Baxter GD, Wright CC: Gender differences in pressure pain threshold in healthy humans. Pain 2003; 101:259–66
Adler LJ, Gyulai FE, Diehl DJ, Mintun MA, Winter PM, Firestone LL: Regional brain activity changes associated with fentanyl analgesia elucidated by positron emission tomography. Anesth Analg 1997; 84:120–6
Wise EA, Price DD, Myers CD, Heft MW, Robinson ME: Gender role expectations of pain: Relationship to experimental pain perception. Pain 2002; 96:335–42
Robinson ME, Wise EA, Gagnon C, Fillingim RB, Price DD: Influences of gender role and anxiety on sex differences in temporal summation of pain. J Pain 2004; 5:77–82
Myles PS, Hunt JO, Moloney JT: Postoperative “minor” complications: Comparison between men and women. Anaesthesia 1997; 52:300–6
Taenzer AH, Clark C, Curry CS: Gender affects report of pain and function after arthroscopic anterior cruciate ligament reconstruction. Anesthesiology 2000; 93:670–5
Fillingim RB: Sex differences in analgesic responses: Evidence from experimental pain models. Eur J Anaesthesiol Suppl 2002; 26:16–24
Mokri B: The Monro-Kellie hypothesis: Applications in CSF volume depletion. Neurology 2001; 56:1746–8
Koss SA, Ulmer JL, Hacein-Bey L: Angiographic features of spontaneous intracranial hypotension. Am J Neuroradiol 2003; 24:704–6
Boezaart AP: Effects of cerebrospinal fluid loss and epidural blood patch on cerebral blood flow in swine. Reg Anesth Pain Med 2001; 26:401–6
May A, Goadsby PJ: The trigeminovascular system in humans: Pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation. J Cereb Blood Flow Metab 1999; 19:115–27
Olah L, Valikovics A, Bereczki D, Fulesdi B, Munkacsy C, Csiba L: Gender-related differences in acetazolamide-induced cerebral vasodilatory response: A transcranial Doppler study. J Neuroimaging 2000; 10:151–6
Karnik R, Valentin A, Winkler WB, Khaffaf N, Donath P, Slany J: Sex-related differences in acetazolamide-induced cerebral vasomotor reactivity. Stroke 1996; 27:56–8
Ebinger F, Kosel C, Pietz J, Rating D: Headache and backache after lumbar puncture in children and adolescents: A prospective study. Pediatrics 2004; 113:1588–92
Geary GG, Krause DN, Duckles SP: Estrogen reduces mouse cerebral artery tone through endothelial NOS- and cyclooxygenase-dependent mechanisms. Am J Physiol Heart Circ Physiol 2000; 279:H511–9
Littleton-Kearney MT, Agnew DM, Traystman RJ, Hurn PD: Effects of estrogen on cerebral blood flow and pial microvasculature in rabbits. Am J Physiol Heart Circ Physiol 2000; 279:H1208–14
Kastrup A, Dichgans J, Niemeier M, Schabet M: Changes of cerebrovascular CO2 reactivity during normal aging. Stroke 1998; 29:1311–4
Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, Tugwell P, Klassen TP: Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet 1998; 352:609–13
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ: Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996; 17:1–12
Balk EM, Bonis PA, Moskowitz H, Schmid CH, Ioannidis JP, Wang C, Lau J: Correlation of quality measures with estimates of treatment effect in meta-analyses of randomized controlled trials. JAMA 2002; 287:2973–82
Clark HD, Wells GA, Huet C, McAlister FA, Salmi LR, Fergusson D, Laupacis A: Assessing the quality of randomized trials: Reliability of the Jadad scale. Control Clin Trial 1999; 20:448–52
LeLorier J, Gregoire G, Benhaddad A, Lapierre J, Derderian F: Discrepancies between meta-analyses and subsequent large randomized, controlled trials. N Engl J Med 1997; 337:536–42
Ioannidis JP, Cappelleri JC, Lau J: Issues in comparisons between meta-analyses and large trials. JAMA 1998; 279:1089–93
LeLorier J, Gregoire G: Comparing results from meta-analyses versus  large trials. JAMA 1998; 280:518–9
Moher D, Pham B, Lawson ML, Klassen TP: The inclusion of reports of randomised trials published in languages other than English in systematic reviews. Health Technol Assess 2003; 7:1–90
Gregoire G, Derderian F, Le Lorier J: Selecting the language of the publications included in a meta-analysis: Is there a Tower of Babel bias? J Clin Epidemiol 1995; 48:159–63
Juni P, Holenstein F, Sterne J, Barlett C, Egger M: Direction and impact of language bias in meta-analyses of controlled trials: Empirical study. Int J Epidemiol 2002; 31:115–23
Wu CL, Hurley RW, Anderson GF, Herbert R, Rowlingson AJ, Fleisher LA: The effect of perioperative epidural analgesia on patient mortality and morbidity in the Medicare population. Reg Anesth Pain Med 2004; 29:525–33
Liu SS, Block BM, Wu CL: Effects of perioperative central neuraxial analgesia on outcome after coronary artery bypass surgery: A meta-analysis. Anesthesiology 2004; 101:153–61
Rodgers A, Walker N, Schug S, McKee A, Kehlet H, van Zundert A, Sage D, Futter M, Saville G, Clark T, MacMahon S: Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: Results from overview of randomised trials. BMJ 2000; 321:1493
Block BM, Liu SS, Rowlingson AJ, Cowan AR, Cowen JA, Wu CL: Efficacy of postoperative epidural analgesia versus  systemic opioids: A meta-analysis. JAMA 2003; 290:2455–63