Archived Comments for:
Efficacy of the epidural blood patch for the treatment of post lumbar puncture headache BLOPP: A randomised, observer-blind, controlled clinical trial [ISRCTN 71598245]
Post-dural puncture headache: pathophysiological issues surrounding CSF leakage and its management with the epidural blood patch
Vinod Gupta, Dubai Police Medical Services, P.O. Box 12005, Dubai, United Arab Emirates
17 July 2005
Oedit and colleagues are well underway with their clinical trial involving use of the autologous epidural blood patch (EDBP) for managing post dual puncture headache (PDPH) [1]. These investigators believe that the placebo effect of EDBP is inconsequential because of the self-limiting nature of PDPH. The likelihood of a significant placebo-effect is the greatest in self-limiting conditions; migraine is a classical example of a self-limiting condition that is very prone to manifest a placebo effect. Second, spontaneous closure of cerebrospinal fluid (CSF) leak is most likely to occur in the first week after the dural puncture. With intervention with the EDBP between 24 hours and 7 days of the symptoms, as in this study [1], we will remain unable to separate the effects of two CSF-leakage reducing / eliminating forces, natural and iatrogenic. To study the effect of the EDBP in PDPH, it may be best to carry out the procedure one week after onset of symptoms in order to eliminate those patients whose CSF-leak is likely to close spontaneously. Third, the nature of the duro-arachnoid lesion (DAL) in PDPH, regardless of the size of the needle or technique of insertion or reinsertion of the stylet prior to withdrawing the needle, is such that the structure of the post-puncture lesion and therefore CSF leakage is not predictable [2,3]. For the same reasons as well as due to the procedural limitations of blind placing of the epidural blood patch that may or may not effectively seal the DAL and stop CSF leakage, the possibility of a cohort with partial sealing and reduced leakage (not eliminated leakage) remains. The placebo effect will most likely affect this cohort, the size of which is completely unpredictable early in the first week. In any case, the placebo effect is not largely or totally dependent on the knowledge whether or not the patient is receiving the blood patch. Fourth, a sham procedure, while creating artificial circumstances [1], is still the most appropriate method to minimize the placebo effect. All clinical trials create artificial conditions, beginning right from the underlying philosophy of the investigator(s), running through communications -- oral or written – including the informed consent, and culminating with the post-procedural analysis that is heavily dependent on mathematical (not biological) logic [4,5]. Informed consent in a clinical trial cannot convey anything beyond the uncertainty of the therapist as well as of the discipline. While patients believe that the trialists, whose grasp of the subject they can but rarely match, are working in their (the patients’) interests, the trialists expect the patients to safeguard their own interests by comprehending the information the trialists select and provide; both assumptions are only partly true. It is a different issue that the selected information provided by the trialists is, in the first instance, incomplete in several ways [4, 5].
None of the factors linked to PDPH including needle size, young age, female sex with lower body mass index, pregnancy or previous PDPH history can be synthesized into a logical hypothesis that predictably explains the particular susceptibility of this sub-population [2, 3]. Whereas simple re-approximation of the cut dural flap to its original position may not stop leakage of CSF, the locally-traumatized and adhesive arachnoid probably seals spontaneously most dural punctures. PDPH might, therefore, be consequential to failure of the arachnoid to seal off the DAL. Quincke needles lessen but do not eliminate the “tent effect” [6] that stretches both the dura mater as well as the arachnoid membrane at the site of the DAL. Due to different biomechanical and tensile properties, rupture of the arachnoid membrane may not always follow the precise anatomical pattern of the dural hole created during lumbar puncture (LP); also partial loss of arachnoid lamina at the site of the DAL is possible. Variable degrees of retraction of the arachnoid membrane at the site of the DAL, as can be seen in the scanning electron microscope pictures presented by Reina et al. [6] may also contribute to prolonged or persistent CSF leakage. If this explanation is truly representative of the biomechanics of the DAL created by LP, use of the same LP needle is unlikely to create identical DAL in different patients; the unpredictability of PDPH in terms of incidence and duration might thus be rationalized [2,3].
There are several pathophysiological issues that can impact the results of clinical trials of EDBP in PDPH [2, 3], whether in sham or non-sham settings. Also, because of patient-related factors that might critically determine CSF-leakage / DAL closure, comparison of the effect of EDBP between diverse patient groups is inappropriate. The highest success rate for EDBP has been reported in obstetric patients [7]. Low incidence of PDPH in spinal anesthesia, obstetric or non-obstetric [8], intriguingly suggests that spinal anesthesia confers a degree of protection from PDPH. In this context, the clinical circumstances surrounding the LP could also be important. Non-obstetric spinal anesthesia is usually preceded by CT- myelograms (and MRI or both) for evaluating underlying clinical conditions possibly correctable by surgery. Myelography is associated with arachnoiditis [9]. Post-myelography, the subclinically inflamed arachnoid may be primed to seal a subsequent DAL more efficiently. Notably, Tourtellotte et al. found the lowest incidence of PDPH for nonobstetric spinal anesthesia (average frequency was 13%)[8]. Furthermore, inducing maximally tolerated dehydration may increase the viscosity of the CSF and possibly reduce susceptibility of women undergoing obstetric spinal anesthesia to develop PDPH; also, there is a greater likelihood that the duro-arachnoid puncture may seal spontaneously in these circumstances [2]. Moreover, dehydration aggravates severity of arachnoiditis induced by aqueous myelography and fluid repletion is recommended before myelography [9]. Paradoxically, dehydration prior to obstetric spinal anesthesia or diagnostic LP may stimulate the arachnoid lamina to seal the DAL more efficiently. Finally, endorphin activity in CSF increases at term pregnancy [10], indicating development of an adaptive antinociception that possibly reduces incidence of PDPH.
Against this background, the recommendation to drink at least 2.0 litres of fluid a day for patients in the control treatment but not for patients in the active limb of the trial [1] is the single most important confounding factor that heavily favours a positive comparative outcome for the EDBP procedure.
References
1. Oedit R, van Kooten F, Bakker SLM, Dippel DWJ: Efficacy of the epidural blood patch for the treatment of post lumbar puncture headache. BLOPP: a randomized, observer-blind, controlled clinical trial [ISRCTN 71598245]. BMC Neurol 2005, 5:12.
2004). Available at: http://jnnp.bmjjournals.com/cgi/eletters/75/6/893
3. Gupta VK: Post-lumbar puncture headache in idiopathic intracranial hypertension. Headache 2004 (In press).
4. Gupta VK: Randomized controlled trials: the hijacking of basic sciences by mathematical logic. BMJ (Published online 6 July 2004). Available at: http://bmj.bmjjournals.com/cgi/eletters/329/7456/2#65969
5. Gupta VK: Trials on clinical trials. BMJ (Published online 30 October 2004). Available at: http://bmj.bmjjournals.com/cgi/eletters/329/7473/996d#82818
6. Reina MA, López A, Badorrey V, De Andrés JA, Martin S: Dura-arachnoid lesions produced by 22 gauge Quincke spinal needles during a lumbar puncture. J Neurol Neurosurg Psychiatry 2004, 75:893-897.
7. Ackerman W, Jeneja M, Kaczorowski D: Prophylactic epidural blood patch for prevention of postdural puncture headache in the parturient. Anesthesiology 1990, 17:45-49.
8. Tourtellotte WW, Haerer AF, Heller GL, et al: Post-lumbar puncture headaches. Springfield, IL: Charles C. Thomas, 1964.
9. Eldevik OP, Haughton VM: Risk factors in complications of aqueous myelography. Radiology 1978, 128:415-416.
10. Lyrenas S, Nyberg F, Willdeck-Lund G, Lindstrom L, Lindberg B, Terenius L: Endorphin activity in cerebrospinal fluid prior to elective cesarean section and in early puerperium. Ups J Med Sci 1987, 92:37-45.
Post-dural puncture headache: pathophysiological issues surrounding CSF leakage and its management with the epidural blood patch
17 July 2005
Oedit and colleagues are well underway with their clinical trial involving use of the autologous epidural blood patch (EDBP) for managing post dual puncture headache (PDPH) [1]. These investigators believe that the placebo effect of EDBP is inconsequential because of the self-limiting nature of PDPH. The likelihood of a significant placebo-effect is the greatest in self-limiting conditions; migraine is a classical example of a self-limiting condition that is very prone to manifest a placebo effect. Second, spontaneous closure of cerebrospinal fluid (CSF) leak is most likely to occur in the first week after the dural puncture. With intervention with the EDBP between 24 hours and 7 days of the symptoms, as in this study [1], we will remain unable to separate the effects of two CSF-leakage reducing / eliminating forces, natural and iatrogenic. To study the effect of the EDBP in PDPH, it may be best to carry out the procedure one week after onset of symptoms in order to eliminate those patients whose CSF-leak is likely to close spontaneously. Third, the nature of the duro-arachnoid lesion (DAL) in PDPH, regardless of the size of the needle or technique of insertion or reinsertion of the stylet prior to withdrawing the needle, is such that the structure of the post-puncture lesion and therefore CSF leakage is not predictable [2,3]. For the same reasons as well as due to the procedural limitations of blind placing of the epidural blood patch that may or may not effectively seal the DAL and stop CSF leakage, the possibility of a cohort with partial sealing and reduced leakage (not eliminated leakage) remains. The placebo effect will most likely affect this cohort, the size of which is completely unpredictable early in the first week. In any case, the placebo effect is not largely or totally dependent on the knowledge whether or not the patient is receiving the blood patch. Fourth, a sham procedure, while creating artificial circumstances [1], is still the most appropriate method to minimize the placebo effect. All clinical trials create artificial conditions, beginning right from the underlying philosophy of the investigator(s), running through communications -- oral or written – including the informed consent, and culminating with the post-procedural analysis that is heavily dependent on mathematical (not biological) logic [4,5]. Informed consent in a clinical trial cannot convey anything beyond the uncertainty of the therapist as well as of the discipline. While patients believe that the trialists, whose grasp of the subject they can but rarely match, are working in their (the patients’) interests, the trialists expect the patients to safeguard their own interests by comprehending the information the trialists select and provide; both assumptions are only partly true. It is a different issue that the selected information provided by the trialists is, in the first instance, incomplete in several ways [4, 5].
None of the factors linked to PDPH including needle size, young age, female sex with lower body mass index, pregnancy or previous PDPH history can be synthesized into a logical hypothesis that predictably explains the particular susceptibility of this sub-population [2, 3]. Whereas simple re-approximation of the cut dural flap to its original position may not stop leakage of CSF, the locally-traumatized and adhesive arachnoid probably seals spontaneously most dural punctures. PDPH might, therefore, be consequential to failure of the arachnoid to seal off the DAL. Quincke needles lessen but do not eliminate the “tent effect” [6] that stretches both the dura mater as well as the arachnoid membrane at the site of the DAL. Due to different biomechanical and tensile properties, rupture of the arachnoid membrane may not always follow the precise anatomical pattern of the dural hole created during lumbar puncture (LP); also partial loss of arachnoid lamina at the site of the DAL is possible. Variable degrees of retraction of the arachnoid membrane at the site of the DAL, as can be seen in the scanning electron microscope pictures presented by Reina et al. [6] may also contribute to prolonged or persistent CSF leakage. If this explanation is truly representative of the biomechanics of the DAL created by LP, use of the same LP needle is unlikely to create identical DAL in different patients; the unpredictability of PDPH in terms of incidence and duration might thus be rationalized [2,3].
There are several pathophysiological issues that can impact the results of clinical trials of EDBP in PDPH [2, 3], whether in sham or non-sham settings. Also, because of patient-related factors that might critically determine CSF-leakage / DAL closure, comparison of the effect of EDBP between diverse patient groups is inappropriate. The highest success rate for EDBP has been reported in obstetric patients [7]. Low incidence of PDPH in spinal anesthesia, obstetric or non-obstetric [8], intriguingly suggests that spinal anesthesia confers a degree of protection from PDPH. In this context, the clinical circumstances surrounding the LP could also be important. Non-obstetric spinal anesthesia is usually preceded by CT- myelograms (and MRI or both) for evaluating underlying clinical conditions possibly correctable by surgery. Myelography is associated with arachnoiditis [9]. Post-myelography, the subclinically inflamed arachnoid may be primed to seal a subsequent DAL more efficiently. Notably, Tourtellotte et al. found the lowest incidence of PDPH for nonobstetric spinal anesthesia (average frequency was 13%)[8]. Furthermore, inducing maximally tolerated dehydration may increase the viscosity of the CSF and possibly reduce susceptibility of women undergoing obstetric spinal anesthesia to develop PDPH; also, there is a greater likelihood that the duro-arachnoid puncture may seal spontaneously in these circumstances [2]. Moreover, dehydration aggravates severity of arachnoiditis induced by aqueous myelography and fluid repletion is recommended before myelography [9]. Paradoxically, dehydration prior to obstetric spinal anesthesia or diagnostic LP may stimulate the arachnoid lamina to seal the DAL more efficiently. Finally, endorphin activity in CSF increases at term pregnancy [10], indicating development of an adaptive antinociception that possibly reduces incidence of PDPH.
Against this background, the recommendation to drink at least 2.0 litres of fluid a day for patients in the control treatment but not for patients in the active limb of the trial [1] is the single most important confounding factor that heavily favours a positive comparative outcome for the EDBP procedure.
References
1. Oedit R, van Kooten F, Bakker SLM, Dippel DWJ: Efficacy of the epidural blood patch for the treatment of post lumbar puncture headache. BLOPP: a randomized, observer-blind, controlled clinical trial [ISRCTN 71598245]. BMC Neurol 2005, 5:12.
2. Gupta VK: Post-dural puncture headache: pathophysiological mechanisms. J Neurol Neurosurg Psychiatry (Published online 17 June
2004). Available at: http://jnnp.bmjjournals.com/cgi/eletters/75/6/893
3. Gupta VK: Post-lumbar puncture headache in idiopathic intracranial hypertension. Headache 2004 (In press).
4. Gupta VK: Randomized controlled trials: the hijacking of basic sciences by mathematical logic. BMJ (Published online 6 July 2004). Available at: http://bmj.bmjjournals.com/cgi/eletters/329/7456/2#65969
5. Gupta VK: Trials on clinical trials. BMJ (Published online 30 October 2004). Available at: http://bmj.bmjjournals.com/cgi/eletters/329/7473/996d#82818
6. Reina MA, López A, Badorrey V, De Andrés JA, Martin S: Dura-arachnoid lesions produced by 22 gauge Quincke spinal needles during a lumbar puncture. J Neurol Neurosurg Psychiatry 2004, 75:893-897.
7. Ackerman W, Jeneja M, Kaczorowski D: Prophylactic epidural blood patch for prevention of postdural puncture headache in the parturient. Anesthesiology 1990, 17:45-49.
8. Tourtellotte WW, Haerer AF, Heller GL, et al: Post-lumbar puncture headaches. Springfield, IL: Charles C. Thomas, 1964.
9. Eldevik OP, Haughton VM: Risk factors in complications of aqueous myelography. Radiology 1978, 128:415-416.
10. Lyrenas S, Nyberg F, Willdeck-Lund G, Lindstrom L, Lindberg B, Terenius L: Endorphin activity in cerebrospinal fluid prior to elective cesarean section and in early puerperium. Ups J Med Sci 1987, 92:37-45.
Competing interests
None declared