An interlaminar epidural is the simplest approach to epidural injection. This approach has been used without x-ray guidance for the past years to create surgical anesthesia, stop the pain of labor and to treat acute and chronic spinal pain conditions like disc herniation. The advent of fluoroscopic guidance real time x-ray imaging in the s allowed pain specialist physicians to precisely target interlaminar epidurals to specific spinal levels and today the interlaminar approach is used throughout the cervical, thoracic and lumbar spine.
Interlaminar epidurals can be performed with minimal discomfort because the needle is placed into the back side of the spine, far away from the irritated spinal nerve roots and the medication indirectly targets the disc-nerve root interface which is in the front and side of the spinal canal.
Back to all Epidural Steroid Injections. To target irritated spinal nerve roots more directly, pain specialist physicians are increasingly using the transforaminal approach to epidural injection. Transforaminal epidural injections are technically more difficult than interlaminar epidurals, require fluoroscopic guidance and are sometimes done at more than one level in a single procedure. Transforaminal epidural injections deposit medication directly onto irritated spinal nerve root so it may be more effective but may also be more uncomfortable compared to interlaminar technique.
Safety Procedures. In addition to relieving pain, the process of natural healing can occur more quickly once the inflammation is reduced. Spinal nerves can become inflamed due to irritation from a damaged disc or from contact with a bone spur. There is a membrane called the dura covering the nerve roots in the spine. Around the dura is a sleeve-like space called the epidural space.
Before nerves can travel from the spine into the arms, chest, and legs, they travel through the epidural space, and exit through small nerve holes. The medication from the epidural steroid injection is placed in the epidural space.
The procedure usually takes approximately 30 minutes, followed by about 45 minutes of recovery time at the clinic. On the day of the epidural steroid injection the patient should not drive. Rest is needed and strenuous activities must be avoided on the day of the epidural steroid injection.
Following the epidural injection, some partial numbness from the anesthetic may occur in the patient's arms or legs. Any partial numbness usually subsides after a few hours. Any remaining pain needs to be reported to the physician, and ideally the patient should keep a "pain diary" to record the pain relief experienced over the next week. There may be an increase in the patient's pain that may last for up to several days. This may occur after the numbing medicine wears off but before the steroid has had a chance to work.
Ice packs may help reduce the inflammation and will typically be more helpful than heat during this time. Improvements in pain will generally occur within 10 days after the epidural injection, and may be noticed as soon as one to five days after the injection. Regular medicines may be taken after an epidural steroid injection. On the day following the procedure, the patient may return to his or her regular activities.
You may be sitting with your back curved or lying on your side on the table in the fluoroscopy room. Your lower back will be cleansed with an antiseptic solution and your skin will be numbed with a local anesthetic in the area of your tailbone.
The physician will use fluoroscopy x-ray to guide the placement of the needle into the epidural space. The needle may not be placed in the exact same site as your pain. In some instances, the physician may inject a local anesthetic with the steroid. You may feel some pressure in your back area along with some re-creation of your pain symptoms during the injection. The doctor will inject the medication slowly in order to decrease your discomfort.
How long does the procedure take? Approximately 20 minutes. Contraindications for procedure. Bleeding problems, infection, or pregnancy. A band-aid will be applied at the injection site. An interlaminar epidural injection is a medical treatment that transports steroids to the roots of the spinal nerves. These types of epidurals come in three different varieties: a cervical epidural injection, a lumbar epidural injection, and a thoracic epidural lumbar injection.
The steroids administered into the spinal nerve roots help combat the inflammation and pain associated with back, leg, arm, and shoulder issues. Injured discs or bone spurs cause inflammation of the spinal nerves. This often results in a high level of pain and discomfort, and the need for a steroid epidural injection becomes vital to starting the healing process.
In an interlaminar epidural injection, the steroids target the nerve roots and may also instigate a process of detoxification, in which inflammatory proteins in the affected area are flushed out of the body. The injection also significantly lessens inflammation and pain, thereby supporting the commencement of the body's natural healing processes.
The interlaminar epidural injection works by entering into the area around the dura membrane, which envelops the spinal nerves. All nerves that journey from the spine into the arms, legs, and chest pass through this area. During injection, the needle is inserted directly into the membrane, delivering steroids to the small space.
In the interlaminar epidural injection process, an IV first conveys an anesthetic so the body can be relaxed for the injection.
It works by delivering steroids directly to the painful area to help decrease the inflammation that may be causing the pain. It is thought that there is also a flushing effect from the injection that helps remove or "flush out" inflammatory proteins from around the structures that may cause pain. In addition to relieving pain, the process of natural healing can occur more quickly once the inflammation is reduced.
Spinal nerves can become inflamed due to irritation from a damaged disc or from contact with a bone spur. There is a membrane called the dura covering the nerve roots in the spine. Around the dura is a sleeve-like space called the epidural space. Before nerves can travel from the spine into the arms, chest, and legs, they travel through the epidural space, and exit through small nerve holes.
The medication from the epidural steroid injection is placed in the epidural space. The procedure usually takes approximately 30 minutes, followed by about 45 minutes of recovery time at the clinic. On the day of the epidural steroid injection the patient should not drive. Rest is needed and strenuous activities must be avoided on the day of the epidural steroid injection.
Following the epidural injection, some partial numbness from the anesthetic may occur in the patient's arms or legs. Any partial numbness usually subsides after a few hours. Any remaining pain needs to be reported to the physician, and ideally the patient should keep a "pain diary" to record the pain relief experienced over the next week. There may be an increase in the patient's pain that may last for up to several days.
This may occur after the numbing medicine wears off but before the steroid has had a chance to work. Ice packs may help reduce the inflammation and will typically be more helpful than heat during this time. Improvements in pain will generally occur within 10 days after the epidural injection, and may be noticed as soon as one to five days after the injection.
Safety Procedures. Interlaminar Epidural Injection An interlaminar epidural is the simplest approach to epidural injection. View an example of an interlaminar epidural injection in the lumbar spine. Transforaminal Epidural Injection To target irritated spinal nerve roots more directly, pain specialist physicians are increasingly using the transforaminal approach to epidural injection.
View an example of a transforaminal epidural injection in the lumbar spine. Do you have questions? We can help! Call to schedule an appointment or to speak with a pain management expert. Take the first step toward a better life Start today by requesting an appointment through our secured online form.
Writing down your side effects can help you provide a complete record to our doctor upon a follow-up call or visit. Are you experiencing lower back pain? The physicians at Spine Institute of North America can assist you with this. We offer patients like you the least-invasive spinal procedures to treat their pain.
Contact us today for more information or to set up an appointment. Use our interactive tool to learn more about treatment for your pain points. Edward Alexeev, M. Salah Mohamed, M. What Is a Lumbar Interlaminar Epidural? How does the process work? There are five main steps: The doctor will have you lay on your stomach on top of two pillows. They will clean and numb the injection site. The doctor uses an X-ray to determine the correct path for the thin needle.
They insert a syringe and inject a bit of dye so they can see where the medication will go. They inject the steroid next. Is fire hot or cold? What Is Recovery Like? Watch for post-injection symptoms, such as: A fever above degrees Fahrenheit Draining or swelling at the site of the injection Pain that increases as the days go on What Are the Lumbar Interlaminar Epidural Steroid Injection Side Effects?
Lumbar interlaminar and transforaminal epidural injections are used in the treatment of lumbar radicular pain and other lumbar spinal pain syndromes. Complications from these procedures arise from needle placement and the administration of medication. Potential risks include infection, hematoma, intravascular injection of medication, direct nerve trauma, subdural injection of medication, air embolism, disc entry, urinary retention, radiation exposure, and hypersensitivity reactions.
The objective of this article is to review the complications of lumbar interlaminar and transforaminal epidural injections and discuss the potential pitfalls related to these procedures. We performed a comprehensive literature review through a Medline search for relevant case reports, clinical trials, and review articles.
Complications from lumbar epidural injections are extremely rare. Most if not all complications can be avoided by careful technique with accurate needle placement, sterile precautions, and a thorough understanding of the relevant anatomy and contrast patterns on fluoroscopic imaging.
Lumbar epidural steroid injections have been used in the treatment of lumbar radicular pain and other spinal pain syndromes [ 1 — 4 ]. The goal is to deliver steroids and anesthetics into the epidural space around the spinal nerves and other spinal structures. By definition, an interlaminar injection is an approach to the dorsal epidural space going through the space between the lamina of the vertebrae.
A transforaminal injection is an approach toward the epidural space via the intervertebral foramen where the spinal nerves exit. The epidural space surrounds the dural sac and is bounded by the posterior longitudinal ligament anteriorly, the ligamentum flavum and the periosteum of the laminae posteriorly, and the pedicles of the spinal column and the intervertebral foramina containing their neural elements laterally.
The space communicates freely with the paravertebral space through the intervertebral foramina. The epidural space contains loose areolar connective tissue, semi-liquid fat, lymphatics, arteries, an extensive plexus of veins, and the spinal nerve roots as they exit the dural sac and pass through the intervertebral foramina [ 5 — 7 ]. The anatomy of the lumbar intervertebral foramen is complicated. It is formed by the pedicles of adjacent vertebrae above and below, the vertebral body of the superior and inferior vertebrae mostly of the superior vertebra and intervertebral disc anteriorly, and the articular processes forming the zygapophyseal joint posteriorly.
The fascia and psoas muscle form the lateral border, while the medial border contains the dural sleeve [ 8 , 9 ]. The foramen allows for the passage of the spinal nerve, the dorsal root ganglion, the segmental spinal artery, the communicating veins between the internal and external plexuses, the recurrent meningeal sinu-vertebral nerves, and the transforaminal ligaments [ 8 , 9 ]. The vascular anatomy of the spinal cord is segmental and based on the embryological development of the body [ 10 , 11 ].
At the start of embryological development, each segmental artery has a branch that supplies the spinal cord. During development most of these branches regress leaving a few left behind to provide blood for the spinal cord. Of those that remain 4—8 will supply the anterior spinal artery and 10—20 will supply the posterior spinal arteries [ 10 , 11 ].
The radiculopial artery branches into the posterior spinal arteries. The radiculomedullary artery branches into the anterior spinal artery. Of particular interest is the artery of Adamkiewicz, which is the largest radiculomedullary artery and major supplier of the anterior spinal artery in the lumbar region. Its origin is highly variable [ 15 ] and in a minority of people may arise from the lower vertebrae in the lumbar spine [ 16 ] and rarely as low as S1. To reach the optimal target area for an interlaminar epidural steroid injection ILESI , a paramedian or midline approach is used through the space between the lamina of the vertebrae.
The needle first penetrates the skin, then subcutaneous tissue, paraspinal muscles, and then finally the ligamentum flavum. The brown circle marks the target point for the subpedicular approach, the blue circle for the retroneural approach, and the pink circle for the retrodiscal approach. The subpedicular and retroneural approaches have the same target point on AP view.
It lies at the bottom of the silhouette of the L4 pedicle P , but is overlapped by the lateral margin of the L4 lamina [ 18 ]. The retrodiscal approach target is lateral to the L5 superior articular process black arrow which is not clearly seen on AP imaging. The lamina has been rotated medially to expose the target points for all three approaches. The subpedicular and retroneural approaches have the same target point on oblique view.
The retrodiscal target point is more easily identified on oblique view black arrow. The subpedicular approach target area lies on the back of the L4 vertebral body. The retroneural approach target area lies more dorsal in the L4—L5 foramen underneath the L4 pedicle P. The retrodiscal approach target area lies just dorsal to the L4—L5 disc space. The brown needle illustrates the subpedicular approach, the blue needle shows the retroneural approach, and the pink needle depicts the retrodiscal approach.
The retrodiscal approach target is lateral to the L5 superior articular process SAP. The retrodiscal approach target is lateral to the L5 SAP overlapped by the brown needle. The retrodiscal approach target area lies just dorsal to the L4—L5 disc. Needles placed underneath the right L3, L4, L5, and S1 pedicles.
Black arrow highlighting exiting right L4 spinal nerve. The retroneural TFESI approach describes the optimal target area more dorsal in the intervetebral foramen compared to the subpedicular technique [ 18 ]. The target typically lies at the intersection of two lines: a longitudinal one between the posterior and middle third of the intervertebral foramen, and a transverse one between the upper and middle third of the intervertebral foramen [ 18 ] Figs.
The retrodiscal TFESI approach places the needle past the lateral surface of the superior articular process SAP into the intervertebral foramen; this technique is similar to the needle approach used in discography, but without cannuating the disc [ 19 ] Figs. In this latter technique, the exiting spinal nerve is lateral rather than medial to the needle as in the subpedicular and retroneural techniques.
The incidence of complications described in the literature with these epidural techniques is low [ 20 , 21 ]. A thorough understanding of the relevant anatomy and potential pitfalls is necessary to avoid most if not all complications.
Complications are related either to the procedure itself—mostly inadvertent placement of the needle off target—or the administration of the corticosteroid or local anesthetic. The purpose of this paper is to review these complications and discuss the potential pitfalls related to these procedures.
Severe infections are noted to be rare with an incidence of 0. They vary between meningitis [ 23 , 24 ], epidural abscess [ 23 , 25 , 26 ], osteomyelitis [ 27 , 28 ], and discitis [ 29 ]. Staphylococcus aureus is the most common organism reported to be found. It is believed to be introduced via the skin through needle puncture.
It is usually introduced due to poor sterile technique. Neurological deficits can occur due to compression from exudate [ 30 ]. Patients with immunocompromising conditions such as diabetes are more susceptible to infection and should be followed closely [ 30 ].
Infection from gram-negative anaerobes can theoretically occur by unintentional penetration into the intestinal or pelvic cavity [ 22 ]. The needle can unintentionally go through the dorsal foramen and past the ventral foramen entering the pelvic cavity Fig. In Fig. With this technique there may be a lack of bony structure to stop needle advancement.
Lateral imaging Fig. If this should occur, i. White arrow shows needle tip. Green line delineating the dorsal sacral border. Red line delineating the ventral sacral border. White arrow illustrating the tip of the needle in the pelvic cavity of a cadaveric specimen.
In the other lumbar TFESIs there is potential to go past the foramen, along the lateral border of the vertebral body, and into the abdominal cavity potentially piercing the intestinal cavity. The needle is advanced laterally to avoid the SAP. If advanced too far lateral the needle tip can end up along the lateral aspect of the vertebral body instead of more medial into the intervertebral foramen. Lateral imaging helps to further confirm the depth of the needle. If the needle depth goes past the anterior border of the vertebral body, it can potentially pierce the intestinal cavity.
However; one must be alerted to this possibility. Once again, if the needle happened to be too far anterior, we recommend discarding the needle rather than repositioning more posterior and medially to minimize the chance of introducing iatrogenic infection. Piercing a vessel is an inherent risk to all injection procedures. Potential complications associated with this are bleeding, the formation of hematomas, and intravascular injection of medication. The potential for bleeding and hematoma formation is increased in patients with a coagulopathy, liver disease, or in patients that take anticoagulant medications such as warfarin or clopidogrel [ 22 , 31 ].
Damage to the underlying vessels may lead to hematomas that cannot be visualized under traditional fluoroscopy. Patients use chronic anticoagulant therapy for the prevention of myocardial ischemia or stroke, thromboprophylaxis after surgery, or treatment of acute thromboembolism [ 32 ]. The intensity and duration of anticoagulation affect the risk of spontaneous, as well as procedural-related spinal bleeding [ 32 , 33 ]. This risk is increased significantly with the use of multiple anticoagulants [ 32 , 33 ].
Warfarin therapy should be discontinued 4—5 days before spinal procedures and the international normalized ratio INR should be within normal range at the time of the procedure to ensure adequate levels of all vitamin K-dependent factors [ 32 , 34 ]. Thienopyridine derivatives, e.
Aspirin and non-steroidal antiinflammatory drugs NSAIDs have not been found to have any contraindications for spinal procedures [ 32 , 34 , 35 ]. Low-molecular weight heparin LMWH should be held for at least 12 h before the procedure in thromboprophylactic dosing and at least 24 h in therapeutic dosing [ 32 , 34 ]. The incidence of epidural hematoma is approximated to be less than 1 in , epidurals [ 34 ].
The actual incidence of neurologic dysfunction resulting from hemorrhagic complications is unknown [ 34 ]. Epidural hematomas can lead to compression of the spinal nerve or nerves causing irreversible damage [ 36 ]. Nerve injury may be minimized by evacuation of the hematoma within 24 h of the first symptoms [ 37 ].
The patient had a myelogram 2 weeks prior to the epidural injection at a different facility, which presumably led to the unrecognized epidural hematoma. Upon injection of contrast, an unusual dye spread occurred. Later, a magnetic resonance imaging MRI of the lumbar spine was obtained demonstrating the epidural hematoma. The contrast spread, in essence, is an epidural hematogram.
Fortunately, images were saved documenting that the hematoma must have existed prior to the epidural injection rather than because of the epidural injection. Interlaminar epidural depicting epidural hematomagram white arrows. Black arrow placed to highlight needle location. Recognition of intravascular uptake and contrast spread is needed to avoid inadvertent injection of medications into the vascularity.
Furman et al. With ILESIs, intravascular uptake is more common with needle placement in the lateral portion of the spinal canal than midline because the internal posterior vertebral venous plexus within the epidural space is located predominantly dorsolaterally [ 39 ]. It is postulated that there is not enough pressure in the venous system to result in spontaneous blood flow into the needle hub.
However, during contrast or medication injection, there is enough positive pressure to keep these smaller vessels distended, resulting in intravascular injection [ 38 , 40 , 41 ]. Therefore contrast injection is essential to minimize subsequent intravascular injection of medications [ 38 ]. Intravascular uptake is twice as likely to occur in patients over 50 years of age [ 40 ].
In the studies that reported the incidence of intravascular injections, no complications or adverse affects were found from intravascular, presumably intravenous, injection of contrast, steroid, or local anesthetic. Theoretically, patients may experience temporary adverse reactions from systemic uptake of local anesthetics. These symptoms include a range of minor symptoms: dizziness, tinnitus, disorientation, muscle twitching, and metallic taste to major symptoms: seizures, unconsciousness, and coma.
The severity of symptoms depends on the amount of local anesthetic used [ 42 ]. Intravenous uptake of medications may also diminish the efficacy of epidural injections [ 38 ]. While intravenous penetration is relatively common with minimal sequelae, intraarterial penetration and subsequent injection of particulate steroids can lead to a catastrophic outcome.
This occurs via the artery of Adamkiewicz which travels with the nerve root through the neural foramen and supplies the anterior spinal artery. This can lead to a spinal infarction and paraplegia [ 12 , 13 , 44 ]. Use of contrast before injection helps to avoid this complication by being able to distinguish an epidural spread versus an intravascular spread.
Houten et al. In each instance, penetration of the vessel was undetected, i. In two procedures the needles were placed transforaminally, one at L3—4 on the left and one at L3—4 on the right, and in the third the tip of the needle was placed immediately lateral to the S1 nerve root [ 12 ]. Some injectionists utilize digital subtraction angiography DSA to help distinguish intraarterial injection of contrast and thus avoid further injection of local anesthetic or steroids into the arterial system.
DSA is a computer-assisted X-ray technique that separates and removes images of bone and soft tissue to permit visualization of vascular structures. DSA, however, is not routinely available in most facilities. There has yet to be any reported complications with this preparation. This may be due to its non-particulate nature [ 45 ]. Derby et al. Theoretically, these attributes should lower the risk of embolic infarcts or prevent them from occurring after intraarterial injection [ 45 ].
There may be a trade off in the efficacy of this non-particulate steroid in that it has a shorter duration of action. Dreyfuss et al. Since particulate steroids have been associated with spinal cord infarctions [ 12 , 44 , 47 ], perhaps a safer yet less efficacious non-particulate steroid should be used [ 46 ]. Since the optimal target area places the tip of the needle more dorsal in the intervertebral foramen, there is less risk of pinning a spinal artery against the posterior wall of the vertebral body or injecting into it.
Direct trauma to a spinal nerve or dorsal root ganglion by a needle is another complication of inadvertent needle placement, especially when performing TFESIs. Severe pain is caused with this trauma so it is important not to over sedate the patient so that this complication is not masked. If severe pain accompanies needle placement, then the needle should be slightly withdrawn and its position reassessed [ 18 ].
Caution should be used such that the anesthetic is not forcibly injected. Furthermore, staying more posterior in the foramen, i. The retrodiscal approach may also reduce the incidence of nerve trauma relative to the classic subpedicular approach in that the nerve may rest further from the target point Fig. The drawback to the retrodiscal approach may be a less recognizable epidural spread of contrast compared to the other classic approaches.
These phenomena, to our knowledge, have not been formally reported or studied. Dural puncture can occur with ILESIs when the needle is advanced beyond the dorsal epidural space, thereby entering the central spinal canal. Dural puncture has also been reported with TFESIs via penetration of the dural sleeve that surrounds the exiting spinal nerves [ 48 ]. Cerebral spinal fluid CSF flashback is typically used to recognize the complication of a dural puncture. Recognition of epidural contrast spread versus subdural and subarachnoid contrast spread patterns is essential because dural penetration may not be accompanied by CSF flashback.
Figure 6 illustrates dural puncture during a TFESI with subdural spread of contrast in a previously reported case study [ 48 ]. Right L4 and right L5 transforaminal epiduragrams are illustrated white arrows [ 43 ]. If local anesthetics are injected intrathecally, blockade of neural elements can result in central canal, cauda equina, and conus medularis syndromes depending on the level of penetration and blockade.
Other reported complications with intrathecal injections of medications include persistent parathesias, arachnoiditis, and meningitis. The amount of local anesthetic typically used in lumbar epidurals 6—8 ml usually is not sufficient enough to cause respiratory depression.
However, a larger volume within the subdural space can ascend rapidly in a cephalad direction causing serious cardiovascular and respiratory effects [ 48 , 53 , 54 ]. Chauhan et al. A 20 ml injection of 1. Dural punctures may also lead to spinal headache. These headaches are typically severe, dull, non-throbbing pain, and fronto-occipital in location, that aggravate in the upright position and diminish in the supine position.
CSF can leak through the dural puncture leading to a loss of CSF pressure and a drop in brain volume. The mechanism producing the headache is unclear, though two theories do exist. First, in an upright position there is tension on the meninges and other intracranial structures which have nociceptors causing pain [ 55 ]. Secondly, it is thought that in the upright position more CSF is forced to exit the dural puncture and the body compensates by venodilation causing pain related to vascular distension [ 55 ].
One possibility is placing the needle both epidurally and intravascularly without a blood flash back. A subsequent injection of air can then cause an air embolism to develop within the vasculature. MacLean and Bachman [ 56 ] depicted a case of syncope, arrhythmia, cardiac ischemia, and neurologic deficit after a spinal epidural injection which caused an arterial gas embolus. There is also the possibility of injecting excessive air epidurally to mimic a mass lesion. Ammirati and Perino [ 57 ] documented a case of new neurological symptoms occurring immediately after a lumbar epidural.
An MRI revealed trapped air displacing the dural sac. Attention should be paid to the amount of air being injected during epidurals to limit this problem. Finn and Case [ 58 ], for example, recounted a case of disc entry as a complication of transforaminal injection.
Though this occurrence is rare, we do not consider this a complication because anecdotally we have found excellent outcomes with injecting around the spinal nerve and into the disc herniation simultaneously. AP image of a left L5 transforaminal sequestered disc injection.
Red arrow depicting needle tip placement. Urinary complications occur more commonly in elderly males, multiparous females, and patients who had inguinal and perineal surgery [ 22 ]. The administration of local anesthetics around the lumbar and sacral nerve roots has a higher incidence of urinary retention [ 59 ].
Epidural block of S2—S4 root fibers decreases urinary bladder tone and inhibits the voiding reflex [ 60 ]. The risk of fluoroscopic exposure to the patient is minimal for one or several isolated fluoroscopic guided epidurals [ 22 ]. A properly calibrated digital fluoroscopy machine delivers a low dose of ionizing radiation.
It is the cumulative exposure to the physician, nurses, radiology technicians, and anyone else that is routinely involved in these procedures that are at risk for complications [ 61 — 63 ]. Possible complications are cancer, sterility, cataract development, bone marrow suppression, and skin desquamation.
Manchikanti et al. The radiation exposure to the physician on the outside of the lead apron over the upper chest was 1, mrem for the entire period. Exposure for 2, procedures extrapolated to 2, mrem outside the apron which is within the annual limits of exposure [ 63 ]. There are many ways to limit the amount of exposure to the patient, physician, and staff.
Fishman et al. Radiation dissipates at the inverse square of the distance from the fluoroscopy tube. Therefore, standing six feet or more from the tube reduces excessive exposure [ 59 — 63 ]. The fluoroscopy anode should be kept under the procedure table thus the patient absorbs the bulk of the directed radiation [ 63 , 65 ]. Intermittent fluoroscopy, last image hold, and pulsed fluoroscopy are ways to reduce radiation times [ 66 ].
According to Fishman, Manchikanti, et al.