Post-dural puncture headache: pathogenesis, prevention and treatment D. K. Turnbull1* and D. B. Shepherd1 2 1Academic Anaesthetic Unit, University of Sheffield, K Floor, Royal Hallamshire Hospital, and 2Jessop Hospital for Women, Sheffield S10 2JF, UK *Corresponding author. E-mail: totleytiger@yahoo.co.uk Spinal anaesthesia developed in the late 1800s with the work of Wynter, Quincke and Corning. However, it was the German surgeon, Karl August Bier in 1898, who probably gave the first spinal anaesthetic. Bier also gained first-hand experience of the disabling headache related to dural puncture. He correctly surmised that the headache was related to excessive loss of cerebrospinal fluid (CSF). In the last 50 yr, the development of fine-gauge spinal needles and needle tip modification, has enabled a significant reduction in the incidence of post-dural puncture headache. Though it is clear that reducing the size of the dural perforation reduces the loss of CSF, there are many areas regarding the pathogenesis, treatment and prevention of post-dural puncture headache that remain contentious. How does the microscopic pattern of collagen alignment in the spinal dura affect the dimensions of the dural perforation? How do needle design, size and orientation influence leakage of CSF through the dural perforation? Can pharmacological methods reduce the symptoms of post-dural puncture headache? By which mechanism does the epidural blood patch cure headache? Is there a role for the prophylactic epidural blood patch? Do epidural saline, dextran, opioids and tissue glues reduce the rate of CSF loss? This review considers these contentious aspects of post-dural puncture headache. Br J Anaesth 2003 91: 718���29 Keywords: anaesthetic techniques, subarachnoid analeptics, caffeine complications, dural puncture complications, headache History Spinal anaesthesia developed in the late 1800s. In 1891, Wynter and Quincke95 aspirated cerebrospinal fluid (CSF) from the subarachnoid space for the treatment of raised intracranial hypertension associated with tuberculous meningitis. The catheters and trochars used were probably about 1 mm in diameter and would certainly have led to a post-dural puncture headache. However, all Quincke and Wynters��� subjects died soon after. In 1895, John Corning, a New York physician specializ- ing in diseases of the mind and nervous system, proposed that local anaesthesia of the spinal cord with cocaine may have therapeutic properties.50 Corning injected cocaine 110 mg at the level of the T11/12 interspace in a man to treat habitual masturbation. Despite being accredited with the first spinal anaesthetic, it is unlikely from his description and the dose of cocaine that his needle entered the subarachnoid space.82 In August 1898, Karl August Bier,137 a German surgeon, injected cocaine 10���15 mg into the subarachnoid space of seven patients, himself and his assistant, Hildebrandt. Bier, Hildebrandt and four of the subjects all described the symptoms associated with post- dural puncture headache. Bier surmised that the headache was attributable to loss of CSF. By the early 1900s, there were numerous reports in the medical literature of the application of spinal anaesthesia using large spinal needles.75 Headache was reported to be a complication in 50% of subjects. At that time, the headache was said to resolve within 24 h. Ether anaesthesia was introduced into obstetric practice in 1847, shortly after Morton���s public demonstration. Despite the obvious advantages of regional anaesthesia for the relief of labour pain, it was not until a Swiss obstetrician in 1901 used intrathecal cocaine for the relief of pain in the second stage of labour that regional anaesthesia for obstetrics was popularized.49 Though both vomiting and a high incidence of post-dural puncture headache were noted, it was the high mortality rate in Caesarean deliveries performed under spinal anaesthesia (1 in 139) that led to the abandonment of this technique in the 1930s. The period from 1930 to 1950 has often been referred to as the ���dark British Journal of Anaesthesia 91 (5): 718���29 (2003) DOI: 10.1093/bja/aeg231 �� The Board of Management and Trustees of the British Journal of Anaesthesia 2003

ages of obstetric anaesthesia���, when natural childbirth and psychoprophylaxis were encouraged. In 1951, Whitacre and Hart59 developed the pencil-point needle, based on the observations of Greene53 in 1926. Developments in needle design since that time have led to a significant reduction in the incidence of post-dural puncture headache. However, dural puncture headache remains a disabling complication of needle insertion into the subarachnoid space. Pathophysiology of dural puncture Anatomy of the spinal dura mater The spinal dura mater is a tube extending from the foramen magnum to the second segment of the sacrum. It contains the spinal cord and nerve roots that pierce it. The dura mater is a dense, connective tissue layer made up of collagen and elastic fibres. The classical description of the spinal dura mater is of collagen fibres running in a longitudinal direction.53 This had been supported by histological studies of the dura mater.93 Clinical teaching based upon this view of the dura recommends that a cutting spinal needle be orientated parallel rather than at right angles to these longitudinal dural fibres. Orientating the needle at right angles to the parallel fibres, it was said would cut more fibres. The cut dural fibres, previously under tension, would then tend to retract and increase the longitudinal dimensions of the dural perforation, increasing the likelihood of a post- spinal headache. Clinical studies had confirmed that post- dural puncture headache was more likely when the cutting spinal needle was orientated perpendicular to the direction of the dural fibres. However, recent light and electron microscopic studies of human dura mater have contested this classical description of the anatomy of the dura mater.102 These studies describe the dura mater as consist- ing of collagen fibres arranged in several layers parallel to the surface. Each layer or lamellae consists of both collagen and elastic fibres that do not demonstrate specific orienta- tion.43 The outer or epidural surface may indeed have dural fibres arranged in a longitudinal direction, but this pattern is not repeated through successive dural layers. Recent measurements of dural thickness have also demonstrated that the posterior dura varies in thickness, and that the thickness of the dura at a particular spinal level is not predictable within an individual or between individuals.102 Dural perforation in a thick area of dura may be less likely to lead to a CSF leak than a perforation in a thin area, and may explain the unpredictable consequences of a dural perforation. Cerebrospinal fluid CSF production occurs mainly in the choroid plexus, but there is some evidence of extrachoroidal production. About 500 ml of CSF is produced daily (0.35 ml min���1). The CSF volume in the adult is approximately 150 ml, of which half is within the cranial cavity. The CSF pressure in the lumbar region in the horizontal position is between 5 and 15 cm H2O. On assuming the erect posture, this increases to over 40 cm H2O. The pressure of the CSF in children rises with age, and may be little more than a few cm H2O in early life. Dura mater and response to trauma The consequences of perforation of the spinal or cranial dura are that there will be leakage of CSF. Neurosurgical experience of dural perforation is that even minor perfor- ations need to be closed, either directly or through the application of synthetic or biological dural graft material. Failure to close the dural perforation may lead to adhesions, continuing CSF leak, and the risk of infection. There are few experimental studies of the response of the dura to perforation.70 In 1923, it was noted that deliberate dural defects in the cranial dura of dogs took approximately one week to close. The closure was facilitated through fibroblastic proliferation from the cut edge of the dura. Work published in 195970 dismissed the notion that the fibroblastic proliferation arose from the cut edge of the dura. This study maintained that the dural repair was facilitated by fibroblastic proliferation from surrounding tissue and blood clot. The study also noted that dural repair was promoted by damage to the pia arachnoid, the underlying brain and the presence of blood clot. It is therefore possible that a spinal needle carefully placed in the subarachnoid space does not promote dural healing, as trauma to adjacent tissue is minimal. Indeed, the observation that blood promotes dural healing agrees with Gormley���s original observation that bloody taps were less likely to lead to a post-dural puncture headache as a consequence of a persistence CSF leak.51 Needle tip deformation and dural perforation It has been proposed that contact with bone during insertion may lead to spinal needle tip deformation.67 90 Damaged needle tips could lead to an increase in the size of the subsequent dural perforation. Recent in vivo studies have demonstrated that the cutting type spinal needle is more likely to be deformed after bony contact than comparable sized pencil-point needles.90 However, no in vivo67 or in vitro work has yet demonstrated an increase in the size of dural perforation where damaged needles are used. Consequences of dural puncture Puncture of the dura has the potential to allow the development of excessive leakage of CSF. Excess loss of CSF leads to intracranial hypotension and a demonstrable reduction in CSF volume.52 After the development of post- dural puncture headache, the presence of a CSF leak has been confirmed with radionuclide cisternography,100 Post-dural puncture headache 719