Effect sizes of causal gene variants are also likely to be small isoniazid 300mg cheap, further reducing the ability of past studies 300mg isoniazid, which are designed to identify larger effect sizes cheap 300 mg isoniazid mastercard, to detect them order isoniazid 300mg free shipping. While the use of meta-analyses may improve statistical power by combining past studies, they are reli- ant on the quality of the original studies. Activin A and its related receptors belong to the transforming growth factor β-family , and are ubiquitously expressed throughout the body, where they mediate numerous cellular functions such as proliferation, differ- entiation, and apoptosis . To identify novel interactions and possible func- tions of susceptibility genes, and prioritize efforts for future functional studies, we previously pursued a novel integrative bioin- formatics approach based on transcriptome profling . Genetic and familial predisposition to eclampsia Obstet Gynecol 32(3):303–311 and preeclampsia in a defned population. Torbergsen T, Oian P, Mathiesen E, Borud O eclampsia across generations: exploring fetal and (1989) Preeclampsia – a mitochondrial disease? Mutze S, Rudnik-Schoneborn S, Zerres K, severe preeclampsia amongst mothers and Rath W (2008) Genes and the preeclampsia mothers-in-law of preeclamptics and controls. Dai B, Liu T, Zhang B, Zhang X, Wang Z (2014) Polymorphisms in infammatory genes (2013) The polymorphism for endothelial are associated with term small for gestational nitric oxide synthase gene, the level of nitric age and preeclampsia. A pre- risk of preeclampsia: an updated meta-analysis eclampsia genome-wide linkage scan in based on 51 studies. New Zealand confrms the presence of a Hum Biol 76(6):849–862 maternal susceptibility locus for preeclampsia, 57. Accessed effect of 10q22 in preeclamptic females coin- 2015 cides with two regions clustered for genes with 71. Wang Q, Wang G, Guo C, Cao X, An L, Du down-regulated expression in androgenetic M, Qiu Y, Yang Y, Wang Y, Wang S, Wang X, placentas. Women who develop hypertensive disorders during pregnancy are considered to have “failed” the cardiovascular stress test of pregnancy and likely represent a subpopulation with inadequate cardiovascular accommodation. Preeclampsia is a serious complication with a myriad of manifestations in both mother and offspring. This pregnancy syndrome is a polygenic disease and has now been linked to a greater incidence of cardiovascular disease. Moreover, offsprings born to preeclamptic mothers exhibit an elevated risk of cardiovascular disease, stroke, and mental disorders during adulthood. This suggests that preeclampsia not only exposes the mother and the fetus to complica- tions during pregnancy but also programs chronic diseases during adulthood in the offspring. The etiology of preeclampsia remains unknown, with various theories being suggested to explain its origin. It is primar- ily thought to be associated with poor placentation and entails excessive maternal infammation and endo- thelial dysfunction. It is well established now that the maternal immune system and the placenta are involved in a highly choreographed cross talk that underlies adequate spiral artery remodeling required for uteroplacental perfusion and free fow of nutrients to the fetus. Although it is not clear whether immuno- logical alterations occur early during pregnancy, studies have proposed that dysregulated systemic and placental immunity contribute to impaired angiogenesis and the onset of preeclampsia. This chapter will focus on important aspects of epigenetics, immunological aspects, and cardio- vascular and vascular remodeling of preeclampsia. It remains a major obstetric concern owing to the associated high prevalence of maternal and fetal mortality and morbidity. Although the etiology is not well characterized, several pathophysiological mechanisms combined have proven to Padma Murthi and Cathy Vaillancourt (eds. All these factors may interact with the genome of the mother and the fetus in terms of gene expres- sion modulation, ultimately affecting the expressed phenotype. The placenta is extremely important for intrauterine fetal development and growth. Early gamete alterations (of epigenetic origin) may be adequate to induce placental defects. Two concepts are mostly accepted: hypertension results either from defects in fetal or placental tissues itself or from a maladapted maternal response to pregnancy. These modifcations typically turn genes on or off, allowing or preventing the gene from being used to make a protein . Exposure to different environmental stimuli (ethanol, oxygen tension, and assisted reproduction technologies), particularly during critical windows of development, results in the formation of adaptive epigenetic marks as part of the adaptive stress response . These are usually established early during development and act as regulators of developmental, tissue, and sex-specifc gene expression . These may be heritable if they occur in the gametes and can have phenotypic consequences in the next generation . Methylation of vital regulatory sites such as gene promoters Epigenetics and Preeclampsia 75 or enhancers is mostly connected to gene repression, resulting in downregulation of gene expression . Therefore, there is a discrepancy between the reported hypomethylated status and the observed downregulated activity of these genes in other studies. It is tempting to speculate that this is a compensatory change in methylation to ensure favorable offspring functioning, but on the other hand, it can be an atypical decrease in gene expres- sion that can lead to metabolic maladaptation. Although this does not prove any causal relationship with long-term health effects, it can be used as an initial proof of concept to conduct new cohort studies . It was clarifed that these molecules are implicated in several diseases, and successful revelation of their role in developmental programming can lead to possible biological biomarkers or targets for therapy . Structural and functional changes in the vas- culature are considered independent risk factors for long-term cardiovascular events [35, 36]. Moreover, distur- bances in endothelial function and high blood pressure may affect arterial elasticity and consequently enhance stiffness . A study postulated the hypothesis that timely arterial hypertrophy could favor a “structural” increase in compliance by decreasing the relative amount of connective tissue . Recently, studies have revealed that both immunological toler- ance and immunocompetent cells are important contributors to normal placentation or spiral artery remodeling by extravillous tro- phoblasts, which establish adequate fow of nutrients to the fetus. Thus, it is believed that overwhelming transgenic gene expression over- rides the control of hypertension and other factors. A substantial increase in sympathetic vasoconstrictor activity occurs, refecting a signifcant burden on the heart, causing changes in cardiac structure and functions . Semin Perinatol 33: Pentinat T, Ramón-Krauel M, Ribó S, Plösch 130–137 T (2012) The role of nutrition on epigenetic 2. Laresgoiti-Servitje E, Gomez-Lopez N (2012) modifcations and their implications on health. The pathophysiology of preeclampsia involves Biochimie 94:2242–2263 altered levels of angiogenic factors promoted 13. Am J Reprod Immunol tion, epigenetic changes at transposons and 63:534–543 imprinted genes, and enhanced susceptibility 4. Nissenbaum J, Bar-Nur O, Ben-David E, molecular pathways suggests a mechanism for Benvenisty N (2013) Global indiscriminate the development of preeclampsia.
Rapid establishment of venous access with large-bore cannulae placed in peripheral veins that drain both above and below the diaphragm is essential for adequate fluid resuscitation in the patient who is severely injured 300mg isoniazid with visa. When vascular collapse and extremity injury impair access to arm or leg vessels purchase isoniazid 300 mg amex, percutaneous cannulation of the internal jugular buy discount isoniazid 300mg on line, subclavian discount isoniazid 300mg with amex, or femoral veins 3756 can be performed. Ultrasound guidance may facilitate cannulation of the internal jugular vein and prevent needle entry and infusion of fluids into the pleural space in patients with a large hemothorax. Ultrasound may also be used for infraclavicular access to the axillary vein, the cephalic or basilic veins at the midarm level, or the femoral vein. If necessary, a cutdown to a saphenous or arm vein can be rapidly performed in older children and adults. In children less than 5 years of age, intraosseous cannulation has a high success rate and a low incidence of complications. Infusion rates comparable with those obtained with intravenous lines are possible in small children, although a pressure infusion device may be necessary to achieve adequate flow. However, the success rate of external cardiac massage in hypovolemic trauma victims is likely to be low. A small Foley catheter introduced into the right atrium or, in desperate situations, a large- bore catheter or introducer inserted in the descending aorta can be used for rapid administration of fluids. Some of the survival predictors include injury mechanism, anatomic injury location, extent of physiologic derangement, presenting signs of life, and presence of cardiac rhythm or vital signs. In contrast patients arriving with pulseless blunt injury without signs of life have the least likelihood to survive (0. Signs of life include pupillary response, spontaneous ventilation, presence of carotid pulse, measurable or palpable blood pressure, extremity movement, and cardiac electrical activity. The highest survival with or without intact neurologic function occurred after penetrating thoracic trauma presented with signs of life. Patients presenting pulseless after penetrating extrathoracic injury had more favorable outcome if they had some signs of life than those who did not. Early Management of Specific Injuries Head Injury Approximately 40% of deaths from trauma are caused by head injury, and indeed even a moderate brain injury may increase the mortality rate of patients with other injuries. In nonsurvivors, progression of the damaged area beyond the directly injured region (secondary brain injury) can be demonstrated at autopsy. Thus, of all the possible secondary insults to the injured brain, decreased oxygen delivery as a result of hypotension and hypoxia has the greatest detrimental impact (Table 53-5). However, more than half of the patients with severe head trauma have other injuries that render approximately 15% of them hypotensive. Approximately 30% are hypoxic on admission as a result of central respiratory depression or associated chest injuries. The most common early complications of head trauma are intracranial hypertension, brain herniation, seizures, neurogenic pulmonary edema, 3758 cardiac dysrhythmias, bradycardia, systemic hypertension, and coagulopathy. If consciousness remains depressed despite ventilation and fluid replacement, a head injury is assumed to be present and the patient is managed accordingly. As noted, hypotension is the most important cause of death in the head-injured patient. A baseline neurologic examination should be performed after initial resuscitation but before any sedative or muscle relaxant agents are administered, and this should be repeated at frequent intervals because the patient’s condition may change rapidly. Anesthetic and adjunct drugs may render an adequate neurologic examination impossible; thus, long-acting muscle relaxants, opioids, sedatives, or hypnotics should be given selectively. In this test, the sum of the scores obtained for eye opening, verbal response, and motor activity correlates with the state of consciousness, the severity of the head injury, and the prognosis. A maximally dilated and unresponsive “blown” pupil suggests uncal herniation under the falx cerebri. The presence of similar findings in ocular injuries makes interpretation of pupillary findings difficult when eye and head injuries coexist. However, the pupillary reaction to light is usually more sluggish in the head-injured patient. Subdural hematomas usually have a concave border, whereas epidural hematomas present with a convex outline classically termed a lenticular configuration. These insults cause exacerbation of trauma-induced cerebral ischemia and metabolic derangements, worsening the outcome. The Brain Trauma Foundation and the American Association of Neurological Surgeons have published evidence-based guidelines for the treatment of head-injured patients. Edema tends to occur in injured brain regions regardless of the type of solution administered because of increased permeability of the blood–brain barrier. Much of the focus has been on in-hospital management of patients with brain trauma, but there is increasing interest in the impact of prehospital care on the outcome in these patients. Multiple studies have demonstrated an association between prehospital endotracheal intubation and mortality of patients with severe brain trauma. Acute mannitol toxicity, manifested by hyponatremia, high serum osmolality, and a gap between calculated and measured serum osmolality over 10 mOsm/L, may result when the drug is given in large doses (2 to 3 g/kg) or to patients with renal failure. Mannitol should be used with great care in the presence of hypotension, sepsis, nephrotoxic drugs, or pre- existing renal disease, because these may also precipitate renal failure. It may exacerbate edema in injured areas in which it may easily enter the tissues. The addition of relatively small volumes of hypertonic saline in concentrations between 3% (6 to 8 mL/kg) and 7. It may cause hypernatremia, hyperosmolality, or hyperchloremic acidosis, probably from renal bicarbonate loss secondary to increased levels of chloride (Cl ). Serum concentrations of sodium (Na ) and− + Cl and the patient’s acid–base status should be followed, and the− administration of hypertonic saline should be discontinued if plasma Na+ reaches 160 mEq/L. There have been several studies comparing hypertonic saline and mannitol for brain relaxation during craniotomy. Resuscitation with albumin 5% or 25% provides a sustained improvement in vital signs, but the increase in colloid osmotic pressure produced by these solutions may be associated with an increased risk of mortality. This hypoperfusion seems to be caused largely by increased cerebral vascular resistance, which may be enhanced by hyperventilation. It should be noted that hyperventilation in the severely brain-injured patient may also be associated with acute lung injury. Of course, immediate surgical decompression, especially of epidural hematomas, is an important factor in reducing morbidity and mortality. Over the past several years there has been much debate regarding optimal blood glucose level in critically ill patients. Brain-injured patients are unique members of this group because brain metabolism is altered by the injury and is heavily dependent on glucose. Hypoglycemia (<40 g/dL) may cause metabolic crisis, whereas hyperglycemia (>200 g/dL) can cause detrimental effects through excitotoxicity, oxidative stress, and inflammatory cytokine release.
Egan R cheap isoniazid 300mg online, Hale M buy discount isoniazid 300 mg line, Nasser N buy isoniazid 300mg fast delivery, et al (2011) High sensitivity of immunoﬂuorescence inﬂuenza A+B assay with analyzer buy isoniazid 300 mg on line. J Acquir Immune Deﬁc Syndr 55(Suppl 2):S102–S105 Chapter 4 Antibody Detection: Principles and Applications Yun F. Since the ﬁrst competitive radioimmunoassay was devel- oped over 50 years ago for human insulin detection [1 ] , immunoassays have been developed with emphasis on fast and sensitive detection technologies and automa- tion. Immunoassay for detection of host- produced antibodies directed against microorganisms, particularly viruses, has been one of the most widely used analytical techniques in laboratory medicine [2, 3]. Automation and random access application have been implemented for rapid diagnosis of infectious diseases. Kobayashi Principles and Characteristics of Techniques Successful immunoassays for antibody (Ab) detection rely upon three important factors: (1) the speciﬁc antigen used to capture target antibody; (2) the target antibody if present, and the detector or secondary antibody used for indirect detection of antibody; and (3) the detection method. First two factors are important for the efﬁciency of antigen–antibody complex formation and the third one is about the ability to detect these complexes and is a critical factor for sensitivity and automation. Immunoassays shall have high sensitivity to detect low concentrations of antibod- ies against infectious agents, as well as high speciﬁcity so as to have no cross-recog- nition of antigenically related antigens and produce no false positive results. In reality, a highly sensitive assay has a low chance to produce false negative ﬁndings and is suitable for screening large numbers of samples. The speciﬁc antigens such as the killed or neutralized virus lysate, synthetic peptides, or recombinant proteins are usually developed in research and development phase for speciﬁcity. The principles of antibody detection assays can be grouped according to the method of analysis, such as direct or indirect assays, or competitive inhibition assays. Since most direct immunoassays are used for antigen detection, and most indirect immunoassays can be used as competitive inhibition assays, we only cover the indirect immunoassays in this chapter. The indirect immunoassay, the most commonly used type of immunoassay, is illustrated in Fig. In brief, the capture antigen used can be either bound on solid phase (1A) or microparticle in liquid phase (1B). The detector or the so-called secondary antibody, is conjugated for signal detection. The immunoassays can be grouped into several categories according to the type of detection systems used (Table 4. Enzymes are effective labels because they catalyze chemical reactions, which can produce a signal. Because a single enzyme molecule can catalyze many chemi- cal reactions without being consumed in the reaction, these labels are effective at amplifying assay signals. Colorimetric or Chromogenic Substrate Colorimetric method is the substrate color change that can be detected by naked eye or optic density using a speciﬁc wavelength of light detected by spectrophotometer. Latex agglutination is a photometric immunoassay that is used more in antigen detection than antibody detection and thus is not covered in this chapter. The primary or target antibodies in serum sample can bind to the target or capture antigens immobilized on plate wells by using enzyme-linked detector (or secondary, conjugate) Abs, such as goat, mouse, or rabbit anti-human immunoglobulin G (IgG) Abs. Secondary Ab labeled by chemical con- jugation of an enzyme bounds the immune complex. The enzyme “ﬁxed” on the solid phase through immune complex interacts with the substrate, catalyzes a chemical reaction with a substrate, and yields a colored product that can be visualized and measured by optical density measured by spectrophotometer. The intensity of sub- strate color change is proportional to the amount of enzyme-linked secondary anti- bodies, which is proportional to the amount of primary antibodies in the sample. Some assays use avidin–biotin complexes between Abs and antigens to increase assay sensitivities. Kobayashi 4 Antibody Detection: Principles and Applications 57 green color) in the presence of hydrogen peroxide, which can be seen without a spectrophotometer. The amount of color generated is then measured after a ﬁxed incubation time at a speciﬁc wavelength. The optical density obtained is then related back to the concentration of the antigen in the sample. Conformational antibody test such as immunoblotting method is another technique for antibody detection. In the so-called Western Blot or immunoblot method, the capture antigens such as proteins, peptides, or viral lysates are elec- trotransferred to a nitrocellulose membrane. If target antibodies are present in the specimen, they will bind to the antigens present on the nitrocellulose strips. Rapid antibody detection has been achieved by using lateral ﬂow diffusion (hand- held, portable device) method. Assay uses colloidal gold, carbon, paramagnetic, or color latex beads for visible line in capture zone on the nitrocellulose or nylon membrane. Known as “handheld” assays, lateral ﬂow assays were initially developed for drugs and pregnancy testing , they are simple to use require minimal training, and require no special storage conditions. In most cases, the manufacturer provides simple instructions that include pictures of positive and negative results. The assays are typically designed on nitrocellulose or nylon membranes contained within a plastic or cardboard housing. In the antibody detection format, a capture antigen is bound to the membrane, and a secondary labeled antibody is placed on a sample appli- cation pad. As the sample migrates down the membrane by capillary action, anti- body present in the sample binds to the labeled antigen and is captured as the complex passes. Colloidal gold, carbon, paramagnetic, or colored latex beads are commonly used particles that create a visible line in the capture zone of the assay membrane for a positive result. This is useful particularly when the control line is built in so that general quality control can be performed only once daily. In general, antibody in a test serum binds radiolabeled antigen to form antigen–antibody complex in liquid phase. Radioactivity can be measured by collecting beads after centrifugation and by gamma counter. The continuous production of the intermediate results in the sustained emission of light for photon output signal measured by the luminometer. Using this type of signal enhancement has allowed immunoassays to be developed that are faster and more sensitive than any traditional colorimetric assay. Light intensity is a linear function of the amount of label enzyme, and the luminescence intensity at any time point is a direct measure of the concentration of the enzyme. The low background signal of the system allows a high degree of discrimination between negative and (true) positive serum samples. Amplify by turnover of the chosen substrate, a single enzyme label can convert >107 mole- cules per minute, a millionfold increase. One oxidation event liberates one molecule of label with release of set number of photons. A nonenzymatic system uses direct chemilumines- cent labels which have lower background signals than the enzyme systems, and will typically give rise to very fast times to elicit signals. Luminol reaction is widely used as a chemiluminescent fast or “ﬂash” reaction, but unlike the peroxyoxalate systems does not require an organic/mixed solvent system. The chemiluminescent emitter is a “direct descendent” of the oxidation of luminol by an oxidant in basic aqueous solution. With the acri- dinium ester system, after the immunological binding and subsequent wash step, the signal takes only 2 seconds to develop, compared with 30 min or longer for an enzyme- generated system.
To stop progressive slowing of the heart rate purchase isoniazid 300 mg on line, the underlying cause of bradycardia should be corrected (e buy generic isoniazid 300mg. Atropine is only effective when myocardial electrical activity is present and the bradycardia is of vagal origin cheap isoniazid 300mg free shipping. Currently effective 300mg isoniazid, isoflurane, sevoflurane, and desflurane are used to maintain anesthesia in children. These solutions replaced glucose-containing hypotonic solutions that were associated with perioperative seizures, aspiration, and brain damage after large volumes were administered during surgery. Normal saline is not routinely used as the primary maintenance solution because large volumes may lead to a hyperchloremic metabolic acidosis (nonanion gap type). Although the shift to isotonic salt solutions dramatically decreased the incidence of perioperative hyponatremia, some specific surgeries (e. Infants and children under 2 years of age who may be hypovolemic should be assessed preoperatively to determine the magnitude of their fluid deficit: mild, moderate, or severe. The signs of mild dehydration (5% body weight loss: approximately 50 mL/kg deficit) include poor skin turgor and dry mouth. The signs of moderate fluid dehydration (10% of body weight loss: 100 mL/kg deficit) include sunken fontanel (if present), tachycardia, and oliguria in addition to the signs of mild dehydration. The signs of severe fluid dehydration (15% of body weight loss: 150 mL/kg deficit) include sunken eyeballs, hypotension, and anuria plus the signs of moderate dehydration. Correction of hypovolemia requires staged infusion of iso-osmolar fluid administration. Approximately 50% of the deficit should be replaced in the first hour, 25% in the second, and 25% in the third. Elective Surgery For elective surgery, the traditional calculation for the hourly fluid infusion rate has been based on replacing the triad of fluid deficit during fasting, ongoing maintenance, and blood and third-space losses. In children, a hypotonic glucose-containing solution was used as the maintenance solution at the rate of 4–2–1 mL/kg/hr rule where 4 mL/kg is for the first 10 kg, 2 mL/kg is for the second 10 kg, and 1 mL/kg is for the third 10 kg and any additional body weight thereafter. Holliday and Segar reappraised their 1957 recommendation recently,274 seeking to address the risks associated with both administering hyponatremic solutions to children who were hypovolemic and applying their 4–2–1 fluid infusion rule to isotonic solutions. They reasoned 3107 that the antidiuretic hormone is upregulated in all children who are fasted for elective surgery, presenting with sepsis or an acute inflammatory response, or receiving medications such as opioids and this is the cause of perioperative hyponatremia and water intoxication. To address this problem, they recommended infusing 10 mL/kg/h isotonic solution for each hour for 2–4 h (except for those with cardiac or renal failure) after induction of anesthesia to re-establish euvolemia and downregulate the antidiuretic hormone. For third-space losses, the replacement volume is based on the severity of the losses: 1 to 2 mL/kg/hr for minor surgery, 2 to 5 mL/kg/hr for moderate surgery, and 6 to 10 mL/kg/hr for major surgery and large third-space losses. Although most pediatric surgeons are careful to minimize bleeding during surgery, it is important to remain vigilant regarding all blood loss during surgery. This replacement, together with the maintenance requirement, should be logged on the anesthetic record. As the combined volume of balanced salt solution approaches 75 to 100 mL/kg, it is important to consider the possibility of dilutional thrombocytopenia and dilution of coagulation factors; coagulation indices should be measured at this time. To estimate the allowable blood loss during surgery, the following equation is used277: Some modify Eq. Irrespective of which equation is used, the actual Hct should be determined before initiating blood transfusion to ensure that the Hct has actually decreased to the desired level. When initiating a blood transfusion in a child, two formulae provide rough estimates of the amount of blood required to increase the hemoglobin concentration by 1 g%: 4 to 5 mL/kg packed cells and 6 mL/kg whole blood. Although a single study suggested that dexamethasone increases the incidence of postoperative tonsil bleeding, their results are inconsistent with the author’s experience and the subsequent literature. Regional Anesthesia and Pain Management There are numerous regional blocks that may be performed to reduce nociception during and after surgery. Three common neuroaxial blocks performed in children today are caudal, epidural, and spinal blocks and these are described later. There has been a shift from neuroaxial to peripheral nerve blocks, both single-dose and continuous local anesthetic administration for perioperative pain management facilitated by the introduction of ultrasound guidance. Morbidity and mortality associated with regional anesthesia in children is exceedingly small and is not considered a substantive argument against its routine use in skilled hands. Caudal Blockade This block is useful for both lower abdominal and lower extremity surgeries in infants and children (<5 to 6 years) who are undergoing ambulatory surgery. It is usually performed under general anesthesia although in neonates, awake caudal and spinal blocks have been performed using local anesthetic infiltration and/or sedation. Single-shot caudal blocks with local anesthetic alone are commonly performed in ambulatory surgery. These blocks may last 4 to 6 hours, but if adjuvant medications are added, they may last even longer. After induction of anesthesia and once that airway is secured, the child is turned onto the lateral decubitus (the side is determined by the anesthesiologist; left-handed anesthesiologists generally prefer the right lateral decubitus position for the child), and the key anatomic sites on the sacrum are palpated: posterior superior iliac spines and the sacral hiatus subtended by the two sacral cornua (see also Chapter 42, Caudal Block section). The sacrococcygeal ligament traverses the space between the two cornua and the coccyx. The skin is then prepared with antiseptic solution and allowed to dry while local anesthetic is prepared. Once the sacrococcygeal ligament has been pierced, the cannula is laid almost flat against the skin (forming a 10-degree angle of the skin) and advanced 2 to 3 mm through the ligament. If any resistance is felt as the catheter is inserted, it is not within the caudal space and the entire cannula 3110 should be removed and the process repeated. If you are not certain the catheter is in the caudal canal, hold your thumb over the sacral hiatus and inject no more than 0. If resistance or a bulge is felt, desist from injecting fluid; subcutaneous fluid will obscure the anatomy and preclude a successful caudal block. If the catheter is properly positioned, then remove the needle and examine for blood or cerebrospinal fluid leaking out the catheter. Connect the syringe with local anesthetic and inject slowly 2 to 3 mL every 2 minutes, while observing the electrocardiogram. This concentration permits excellent analgesic with motor blockade that resolves within 1 hour of placement. Adjunctive medications have been used to prolong the duration of the caudal block for several hours at best. The catheter is inserted exactly as described above for caudal blocks and the catheter threaded to the spinal level necessary for perioperative analgesia. The catheter should be taped away from the anus or, alternately, tunneled under the skin to the side opposite the surgery. Catheters that are smaller than 21 ga may not thread to the desired dermatome level. Alternative strategies that may be used to achieve the desired level of block include the Tsui approach289 and inserting the catheter at an intervertebral space closer to the level of surgery. To reduce absorption of local anesthetic, epinephrine is routinely added to the 3111 bupivacaine.