Nanakram Agarwal, MD, MPH, FACS

• Professor of Surgery
• New York Medical College
• Chief of Surgical Intensive Care Unit
• Our Lady of Mercy Medical Center
• Bronx, New York

The training of personnel using simulation has been shown to be an effective preparation for the teamwork and communication needed in the emergent situation of a neonatal resuscitation medicine that makes you poop buy compazine 5mg visa. Until more recently medicine hat alberta canada buy compazine 5mg with amex, the availability of adequate models to practice technical skills treatment guidelines buy compazine 5 mg otc. New high-fidelity manikins now available provide much greater realism and anatomic fidelity to solve this problem in training treatment for plantar fasciitis cheap compazine 5mg otc. In some situations medicine quest safe compazine 5 mg, a single competent person is appropriate to the clinical situation medicine xanax discount compazine 5mg visa. At other times, a full resuscitation team of three or more skilled providers is necessary. Even an emergency call for assistance to the neonatal team should include pertinent information. Identifying a high-risk situation before delivery of the infant provides time for adequate preparation and gathering the appropriate personnel in the delivery room. Because of modern obstetric techniques and anesthesia, it is no longer necessary to consider a repeat cesarean section as a high-risk delivery because this form of delivery carries no greater risk than a vertex vaginal delivery. At every delivery, equipment and personnel should be available in case of unanticipated neonatal depression. An area in or near the delivery room should be designated as the resuscitation area, and provisions should be made for adequate space, heat (radiant warmer), blended oxygen, and suction. Supplies and drugs as specified in the resuscitation guidelines should be placed in a code cart or bag or attached to a wall board for easy access. These supplies should be routinely checked by hospital personnel and rechecked for completeness and good working order. A delay in effective resuscitation may occur if someone needs to leave the delivery room during the procedure to obtain an essential piece of equipment. The use of simulation training using manikins and the holding of mock code drills on an ongoing basis help to maintain skills and develop coordination among staff. To minimize the chances of brain damage, one should begin resuscitation as soon as there is evidence that the infant is unable to establish ventilation sufficient to maintain an adequate heart rate. Waiting until a 1-minute Apgar score is assigned before initiating resuscitation only delays potential therapies. An Apgar score at 1 minute of 0 to 3 often indicates the presence of secondary apnea. Infants who fail to achieve an Apgar score of 7 by 5 minutes of age should have repeated Apgar scores every 5 minutes until the score is at least 7. Having trained personnel readily available means having someone present at every delivery who has the skill required to perform a complete resuscitation, with other available staff close at hand in case they are needed. This person does not have to be a physician, but should be able to perform the technical skills and have the cognitive knowledge necessary to initiate the resuscitation process. The hospital is responsible to ensure the competence of these personnel in the same way a surgeon is credentialed to perform certain operations. Adequate training involves more than simply going through a course and receiving a certificate of completion. Finally, the personnel available to the delivery room should be capable of working together as a team. If staff are skilled at carrying out their responsibilities and can Elements of a Resuscitation A resuscitation can be viewed as a series of elements (Box 32-3). The process is not a linear set of steps in which one marches inexorably from one point to another. Parents may be present while perinatal care is being provided to neonates, including procedures, resuscitation, and stabilization. Parents should be informed about and involved in the care of their infants within the principles of familycentered care. In most circumstances, a healthy and vigorous infant does not even require suctioning after delivery. With appropriate triaging and oversight, many, if not most, infants can be given directly to the mother after birth without compromising the infant. A rapid initial assessment that provides the information necessary to triage the infant appropriately is required. If the infant has not passed meconium in utero, is term, is breathing easily, has good tone, and appears normal and vigorous, it may be appropriate to hand the child to the mother for bonding immediately after birth. As the mother holds the infant, a light blanket may be provided to prevent rapid evaporative heat loss while covering the infant in such a way as to be able to observe the infant for signs of increasing distress. If the infant has passed meconium in utero, is preterm, is not breathing easily, has diminished tone, or does not appear normal and vigorous, the infant should be placed on a radiant warmer until a more thorough assessment of the infant can be done. The following steps apply to any infant who is not term, healthy, and vigorous at birth. Evaluation of color at birth is usually not helpful in determining the status of a newborn because it may take several minutes for even a healthy term infant to achieve Spo2 greater than 90% and "become pink" (see Chapter 34). Newborns who do not qualify for routine care should be placed in warm blankets and quickly moved to a preheated radiant warmer set at 100% power. The infant should be thoroughly dried, and the wet blankets should be promptly removed to avoid evaporative heat loss. These simple measures can minimize the decrease in core temperature that the term infant experiences at birth. Because hypoxia blunts the normal response to cold, a hypoxic infant undergoes a greater than normal decline in core temperature if not thermally protected. However, if the newborn is vigorous and born through clear amniotic fluid, this procedure is not necessary14 and stimulation of the posterior portion of the pharynx may induce bradycardia. An infant exposed to meconium in the amniotic fluid represents a special circumstance (discussed in Chapter 35). Through the accumulation of brown fat late in gestation, the term newborn is able to activate thermogenesis by stimuli of oxygenation, ventilation, and oxidative metabolism via various hormonal intermediaries. The lack of brown fat accumulation in preterm infants and the sequelae of asphyxia in term infants put these newborns at significant disadvantage in thermoregulation post delivery. The neonate with a very large surface area-to-mass ratio is susceptible to cold stress; this is especially true for depressed infants with poor perfusion and extremely low birth weight infants. Unintentional hypothermia in neonates has been associated with metabolic acidosis, increased oxygen consumption, and increased mortality, especially in very preterm infants. All babies will be cyanotic at birth and blow-by oxygen is not indicated at this time. Positive pressure ventilation may be given initially in term and latepreterm infants with air (21% FiO2). Continued tactile stimulation is not useful and may be harmful if ineffective maneuvers allow the baby to remain hypoxic and acidotic. The decisions from this point revolve around the response of the infant-primarily heart rate and respirations. Free-Flow Oxygen Over the past several years, there has been considerable discussion and research on the use of oxygen in neonatal resuscitation (see Chapter 34). Studies of normal term newborns have shown, however, that it may take 6 minutes or longer for infants to reach Sao2 greater than 90%, and many clinicians believe the use of oxygen should be restricted unless the baby remains bradycardic. A flow-inflating bag (but not a selfinflating bag) is capable of delivering high concentrations of blow-by oxygen. During an emergency, cold, dry oxygen may be given for a short time; however, if free-flow oxygen is to be continued for any period, it should be heated and humidified and given through wide-bore tubing. An oxygen blender and oximeter are useful in determining the amount of oxygen the infant requires. It is recommended that all hospitals should be capable of blending oxygen in the delivery room and using pulse oximetry in this area. Resuscitation by positive pressure ventilation and tris-hydroxymethyl aminomethane of rhesus monkeys asphyxiated at birth. American Academy of Pediatrics/American College of Obstetricians and Gynecologists. American Academy of Pediatrics, Committee on Fetus and Newborn, American College of Obstetricians and Gynecologists, Committee on Obstetric Practice. Influences of arterial oxygen tension and pH on cardiac function in the newborn lamb. Oronasopharyngeal suction versus no suction in normal and term infants delivered by elective cesarean section: a prospective randomized controlled trial. Resuscitation of the newly born infant: an advisory statement from the Pediatric Working Group of the International Liaison Committee on Resuscitation. Pulmonary hemodynamics in neonatal lambs resuscitated with 21%, 50% and 100% oxygen. Admission temperature of low birth weight infants: predictors and associated morbidities. Body temperature in the immediate neonatal period: the effect of reducing thermal losses. Ultrasound-guided sampling of umbilical cord and placental blood to assess fetal wellbeing. Refining the role of oxygen administration during delivery room resuscitation: what are the future goals Response of the pulmonary vasculature to hypoxia and H+ ion concentration changes. Determinants of the first inspiratory volume and functional residual capacity at birth. Part 11: Neonatal resuscitation: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Establishing a functional residual capacity at birth: the effect of sustained inflation and positive end expiratory pressure in a preterm rabbit model. Over the past 20 years guidelines for those providing care to these infants have been developed. These changes normally occur in the first minutes after birth28 and are accompanied by an increase in pulmonary blood flow and the onset of regular respiration. If a newborn does not quickly establish effective respiration, assistance is immediately required. This is usually brief and limited to respiratory support,39,47 unless there is abnormal anatomy, significant fetal acidemia, or poor application of respiratory support. Preterm lungs are delicate, and lung injury can occur with just a few manual inflations. In the early 1960s, measurements of respiratory activity in healthy newborn term infants showed that the first breaths are characterized by short deep inspiration, followed by a prolonged expiratory phase with a closed, or partially closed glottis. Abdominal muscle contraction pressurizes the chest, further pushing back the air-liquid interface; this is called expiratory braking. Guidelines recommend initial steps of warming, drying, and stimulating the baby, opening, and in some cases clearing the airway. Therefore, large negative pressures are required for initial lung inflation and to drive the air-liquid interface to the distal airways. The negative transpulmonary pressure created by term infants is typically -50 cm H2O, and up to -100 cm H2O. It may be helpful to be aware that: Accurate measurements of oxygen saturation (SpO2) and heart rate can be obtained using pulse oximetry by about 90 seconds of life. Basics of Positive Pressure Support When an infant fails to establish spontaneous breathing after birth, the caregiver must commence positive pressure support. Usually this is initially applied using a face mask and pressure-generating device. The management of preterm neonates who require ongoing respiratory support remains controversial. A review of several recent studies7 and international guidelines58 suggest that both options are appropriate, and recommend that the decision to be guided by local expertise. They are the only devices that can be used without a gas supply and have been shown to be the most effective method for reducing mortality from birth asphyxia in resource-poor areas. Self-inflating bags usually incorporate a valve that limits the maximum pressure that can be delivered. Pressures greater than 100 cm H2O have been reported, resulting in very high delivered volumes, greater than 20 mL/kg. A pressure-limiting valve can be attached to prevent high pressure being inadvertently delivered. Both are preferable to mouth-to-mouth resuscitation, but still carry some risk of infection. Whichever device is used, providers need to be trained in how to set up and use the equipment. Face masks are very commonly used,51 but nasal tubes, laryngeal masks, and endotracheal tubes are also frequently applied. Round, cushion-rimmed masks are used more commonly than anatomically shaped, triangular masks. The peak pressure is achieved by occluding a hole in the top of the device with a finger. Inflation time depends on the length of time the hole is occluded (but is often >0. T-pieces are easy to use, and are preferred by both experienced and inexperienced operators. Variable leaks may result in some tidal volumes that are too low and others that are dangerously large. This pressure may obstruct the airway16 by distorting the nose and altering the position of the mouth and chin. It may assist with the first effective inspiratory volume during transition,6 even if mask ventilation fails to adequately inflate the lungs. To ensure minimal leak when the nasal route is used, it may be necessary to close the mouth, and when a single nasal tube is used, it may also be necessary to occlude the contralateral nostril.

Syndromes

• Blood tests (such as CBC with differential, blood electrolyte levels, and liver function tests)
• Fortulgesic
• Itching -- may become more itchy if infected
• Oxycodone (Oxycontin, Percocet, Percodan)
• Rapid or irregular heartbeats, including atrial fibrillation
• Tenderness and swelling of the arms, legs and sometimes the joints
• Low bone density, seen by dual x-ray absorptiometry (DEXA)
• Difficulty doing daily activities

Muscle weakness is ascertained through observation of spontaneous or sensation-induced movements of the extremities medicine zetia generic 5 mg compazine with amex. Although muscle hypotonia and weakness often occur together treatment zone tonbridge generic compazine 5 mg on-line, hypotonia can be seen in the absence of weakness medicine man dispensary buy generic compazine 5 mg on-line. Indeed treatment 2nd degree heart block purchase 5 mg compazine visa, hypotonia combined with weakness typically denotes an intrinsic disease of the peripheral nervous system (nerve or muscle) treatment centers in mn order compazine in united states online, whereas hypotonia with a preservation of muscle strength denotes a disturbance of the brain or spinal cord georges marvellous medicine cheap compazine 5 mg free shipping. Full-term newborns exhibit both visual and auditory habituation, which is elicited with a bright light and loud bell, respectively. The eyes are sequentially exposed to a bright light at a frequency of about 1 per second; the normal response is an initial strong blink followed by extinction after 3 to 5 exposures. Failure to respond initially to the sensory stimulation or a lack of habituation suggests cortical dysfunction. The limb should be positioned in partial flexion and the appropriate tendon tapped with an infant reflex hammer. The head should be maintained in the neutral position to prevent inducing an asymmetric tonic neck response, which produces asymmetric reflex activity. Typically, upper extremity deep tendon reflexes are more difficult to elicit than lower extremity reflexes. In newborn infants, the Achilles tendon is not tapped directly; the reflex is elicited by tapping a thumb positioned on the plantar surface of the partially dorsiflexed foot. Interpretation of the results of testing deep tendon reflexes is more problematic in neonates than older children but may help to confirm an asymmetric lesion. Eliciting plantar responses is not worthwhile because their interpretation presents problems. Paradoxically, the oculovestibular (caloric) reflex is incomplete before 28 to 30 weeks, with reduced medial displacement of the eye contralateral to the ear canal stimulated with cold water (intranuclear ophthalmoplegia). Corneal and gag reflexes are present in even the small premature infant, as is facial grimacing to nasal stimulation. These reflexes are fully developed and strong in the healthy, full-term newborn and typically disappear in the months to follow. By term, the infant remains alert for prolonged periods during wakefulness and readily responds to visual, auditory, and tactile stimulation. A notable difference in the neurologic status of the premature and full-term neonate is that of muscle tone. The hypotonicity is especially apparent when measuring the popliteal and heel-to-ear angles and when executing the scarf sign. The maturational changes in muscle tone must be taken into account when evaluating newborns of varying gestational ages. When held in vertical suspension, the infant does not extend the head, trunk, or extremities. The maturational change from hypotonia of the small premature infant to the predominantly flexion posture of the full-term infant is manifest first in the legs and later in the arms and head. By 34 gestational weeks, the infant lies in a froglike position while supine; the legs are flexed at the hips and knees, but the arms remain extended and relatively hypotonic. Developmental reflexes appear at specific ages of gestation to become fully developed and strong in the healthy full-term infant (see Table 29-4). The palmar and plantar grasp responses become apparent at about 28 weeks and are strong by 36 weeks. The Moro reflex makes its appearance at 24 to 26 weeks and evolves through 38 weeks, at which age the entire abduction-adduction response is present. Natural history of innocent heart murmurs in newborn babies: a controlled echocardiographic study. Long-term visual acuity and its predictors after surgery for congenital cataract: findings of the British congenital cataract study. Late diagnosis of congenital dislocation of the hip and the presence of a screening programme: South Australia population based study. Do babies with isolated single umbilical artery need routine postnatal renal ultrasonography The neurological assessment of the preterm and full-term newborn infant, Clinics in developmental medicine. The definition of some external characteristics used in the assessment of gestational age of the newborn infant. Lumbosacral skin markers and identification of occult spinal dysraphism in neonates. Impact of pulse oximetry screening on the detection of duct dependent congenital heart disease: a Swedish prospective screening study of 39,821 newborns. Initial evaluation of children with heart murmurs by the non-specialised paediatricians. Assessment of gestational age by examination of anterior vascular capsule of lens. The neurologic examination has been widely studied as a predictor of subsequent neurodevelopmental problems, but it is limited because many abnormal neurologic signs may be transient and because significant neurological abnormalities may take weeks or months to become manifest. However, in spite of its limitations in specificity and in predicting prognosis, the neurologic examination is useful when considered in conjunction with a history suggestive of a neurologic problem and neuroimaging. Neurologic abnormalities that are persistent and marked or asymmetric place the infant at increased risk of neurodevelopmental problems. The neurologic examination may be helpful in delineating the extent of neurologic deficits. Multiple neurologic abnormalities are more likely to be more significant than isolated abnormalities. Pediatric vesicoureteral reflux guidelines panel summary report: clinical practice guidelines for screening siblings of children with vesicoureteral reflux and neonates/infants with prenatal hydronephrosis. The value of the routine chest roentgenogram in the cardiological evaluation of infants and children: a prospective study. Isolated single umbilical artery anomaly and the risk for congenital malformations: a meta-analysis. Non-surgical correction of congenital deformities of the auricle: a systematic review of the literature. Presentation of congenital heart disease in infancy: implications for routine examination. Routine neonatal examination: effectiveness of trainee paediatrician compared with advanced neonatal nurse practitioner. Question 3: Is ultrasonography required to rule out congenital anomalies of the kidneys and urinary tract in babies with isolated preauricular tags or sinuses National cross-sectional study of detection of congenital and infantile cataract in the United Kingdom: role of screening and surveillance. Preauricular skin tags and ear pits are associated with permanent hearing impairment in newborns. They may be avoidable, or they may be unavoidable and occur despite skilled and competent obstetric care, as in an especially hard or prolonged labor or with an abnormal presentation. Fetal injuries related to amniocentesis and intrauterine transfusions and neonatal injuries after resuscitation procedures are not considered birth injuries. However, injuries related to the use of intrapartum monitoring of the fetal heart rate and collection of fetal scalp blood for acid-base assessment are included. Factors predisposing the infant to birth injury include macrosomia, prematurity, cephalopelvic disproportion, dystocia, prolonged labor, abnormal presentation, and certain operative deliveries, particularly vacuum extraction. The fetus may also sustain injury, including death, if the mother is involved in a motor vehicle collision. Although usually protected by maternal soft tissues, the uterus, and amniotic fluid, the fetus may be subjected to the same acceleration-deceleration forces as the mother. This may result in full-thickness bowel injury and fulminant disseminated intravascular coagulation. In 1981, birth injuries ranked sixth among major causes of neonatal death, resulting in 23. Of particular concern are severe intracranial injuries after operative vaginal delivery (vacuum-assisted and forceps delivery) and failed attempts at operative vaginal delivery. Although many injuries are mild and self-limited, others are serious and potentially lethal. This chapter describes conditions that can be managed by observation only, as well as those that require more aggressive intervention. In addition to assuring timely institution of therapy when indicated, recognition and documentation before discharge from the hospital will help avoid inappropriate suspicion of inflicted injury (child abuse) at a later date. Injuries caused by dystocia occur over the presenting part; forceps injury occurs at the site of application of the instrument. Forceps injury frequently has a linear configuration across both sides of the face, outlining the position of the forceps. The affected areas should be kept clean to minimize the risk for secondary infection. These lesions usually resolve spontaneously within several days with no specific therapy. Etiology Petechiae are probably caused by a sudden increase in intrathoracic and venous pressures during passage of the chest through the birth canal. An infant born with the cord tightly wound around the neck may have petechiae only above the neck. Differential Diagnosis Petechiae may be a manifestation of an underlying hemorrhagic disorder. The localized distribution of the petechiae, absence of subsequent crops of new lesions, and a normal platelet count exclude neonatal thrombocytopenia. The platelet count also may be low because of infection or disseminated intravascular coagulation. Infections may be clinically distinguished from traumatic petechiae by the presence of other signs and symptoms. Disseminated intravascular coagulation usually is associated with excessive and persistent bleeding from a variety of sites. Petechiae usually are distributed over the entire body when associated with systemic disease. Etiology Although subcutaneous fat necrosis can occur without any obvious cause, it is most commonly seen in association with perinatal asphyxia. Other etiologic factors that have been implicated include cold exposure, localized skin trauma, obstetric trauma, preeclampsia, gestational diabetes, maternal or fetal risk of thrombosis, maternal cocaine use, hypothermia, prostaglandin E administration, brown fat deficiency, meconium aspiration, sepsis, and intrapartum calcium channel blocker administration. It can also occur as a complication of therapeutic hypothermia for perinatal asphyxia or in newborns undergoing surgical procedures. The distribution of the lesions usually is related to the site of trauma, which explains the frequent involvement of shoulders and buttocks. One suggested mechanism of pathogenesis proposes that diminished in utero circulation and mechanical pressure during labor and delivery result in vascular compromise to specific areas, which eventually causes localized fat necrosis. The incidence is increased in premature infants, especially after a rapid labor and poorly controlled delivery. When extensive, ecchymoses may reflect blood loss severe enough to cause anemia and, rarely, shock. The rise in serum bilirubin that follows severe bruising may be decreased by the use of phototherapy (see Chapter 100). Pathology Histopathologic studies reveal initial endothelial swelling and perivascular inflammation in the subcutaneous tissues. This is followed by necrosis of fat and a dense granulomatous inflammatory infiltrate containing foreign bodyype giant cells with needle-shaped crystals resembling cholesterol. Clinical Manifestations Necrotic areas usually appear between 6 and 10 days of age, but may be noted as early as the second day or as late as the sixth week. They occur on the cheeks, neck, back, shoulders, arms, buttocks, thighs, and feet, with relative sparing of the chest and abdomen. The affected areas may be slightly elevated above the adjacent skin; small lesions may be easily movable in all directions. This condition may be associated with hypoglycemia, hypertriglyceridemia, hypercalcemia, anemia, and thrombocytopenia. Marked symptomatic hypercalcemia may develop in infants with subcutaneous fat necrosis at 3 to 4 weeks of age; this has been characterized by vomiting, weight loss, anorexia, fever, somnolence, and irritability, with serum calcium levels as high as 17. They usually occur on the scalp, buttocks, and thighs, but they may occur on any part of the body. If the wound is superficial, the edges may be held in apposition with butterfly adhesive strips. Deeper, more freely bleeding wounds should be sutured with the finest material available, preferably 7-0 nylon. Rarely the amount of blood loss and depth of wound require suturing in the delivery room. After repair, the wound should be left uncovered unless it is in an area of potential soiling, such as the perineal area; in such locations, the wound should be sprayed with protective plastic. Serum or blood or both accumulate above the periosteum in the presenting part during labor. This extravasation results from the higher pressure of the uterus or vaginal wall on those areas of the fetal head that border the caput. Thus, in a left occiput transverse presentation, the caput succedaneum occurs over the upper and posterior aspect of the right parietal bone; in a rightsided presentation, it occurs over the corresponding area of the left parietal bone. The soft swelling is usually a few millimeters thick and may be associated with overlying petechiae, purpura, or ecchymoses. Because of the location external to the periosteum, a caput succedaneum may extend across the midline of the skull and across suture lines. After an especially difficult labor, an extensive caput may obscure various sutures and fontanelles. Occasionally, a caput succedaneum may be difficult to distinguish from a cephalhematoma, particularly when the latter occurs bilaterally. Careful palpation usually indicates whether the bleeding is external to the periosteum (a caput) or beneath the periosteum (a cephalhematoma). Iatrogenic encephalocele is an infrequent complication of vacuum extraction delivery and may present like a caput succedaneum initially.

Size has an effect on response to anesthetics symptoms gluten intolerance generic compazine 5 mg without a prescription, and developmental age has a profound impact on the dose response symptoms xanax is prescribed for buy compazine discount, distribution medicine remix buy compazine on line, and metabolism of these drugs treatment xerophthalmia 5mg compazine visa. Inhalational Agents Although common in older children symptoms xanax treats order generic compazine, inhalational anesthesia has not been used extensively in premature infants symptoms jock itch purchase compazine in united states online. Use of inhalational agents was thought to be extremely dangerous, and based on reports of hemodynamic instability and cardiovascular collapse, it was believed that neonates would not tolerate these drugs. In reality, these agents can be used safely, although very careful administration is required. The anesthetic effect of inhalational agents depends on the partial pressure of the anesthetic in the brain and the potency of the agent. For several reasons, very high partial pressures of the inhalational agents in the brain develop much more rapidly in neonates than in older children and adults. Second, a greater fraction of the cardiac output in the neonate is distributed to the vessel-rich group and consequently the brain. Finally, the solubility of the inhaled anesthetics in blood is less in neonates than in adults. Common inhalational anesthetics are halothane, isoflurane, sevoflurane, and nitrous oxide. Inhalational anesthetics are complete anesthetics, with analgesic and amnesic properties. In previous years, halothane probably was the most commonly used because it is minimally irritating to the airway, and it can be used for a very smooth mask induction of anesthesia. Halothane is a significant myocardial depressant, however; it sensitizes the heart to catecholamine-induced arrhythmias and is rarely if ever used. In contrast, isoflurane is very pungent and cannot be used for mask induction, but it has less effect on cardiac output than halothane. Systemic vascular resistance is decreased by isoflurane, and hypotension can result, especially if preload is diminished. It is not irritating to the airway, and it is almost insoluble in blood, so that equilibration between brain and alveolus occurs rapidly. Cardiovascular effects are more similar to effects with isoflurane than with halothane. There is little published experience with sevoflurane in preterm infants, although it is used primarily for mask inductions in healthier neonates. There have been no reports, however, of intraoperative or postoperative complications related to sevoflurane and cardiac repolarization abnormalities, and it is uncertain if this is of any clinical concern. The need for oxygen as part of inspired gases prevents achievement of these levels. Insolubility and the high concentration that is necessary for any meaningful effect cause nitrous oxide to enter progressively and to expand any gas-filled space in contact with the circulation, which rapidly leads to bowel distention or expansion of pneumothorax. If ventilation is interrupted for any reason, nitrous oxide also rapidly fills the alveoli, leading to dilution of the alveolar oxygen, producing a hypoxic mixture and rapid desaturation. For these reasons, nitrous oxide is best limited to adjunct use during mask induction, with a switch to an air-oxygen mixture during maintenance anesthesia. As previously discussed, all of the inhalational agents cause neuroapoptosis in animal studies. Intravenous Agents Intravenous agents include sodium thiopental, propofol, ketamine, various narcotics, and benzodiazepines. Sodium thiopental is an ultrahort-acting barbiturate used primarily as an induction agent. There is some evidence that premature neonates are more sensitive to thiopental than older infants, possibly because of decreased binding by serum proteins. Use is limited in smaller and sicker neonates because it has negative inotropic activity and is a peripheral vasodilator. At present, ongoing pharmacy shortages of thiopental have led to a major decrease in usage. Propofol is a phenol derivative supplied as an emulsion in lipid, which in older children and adults is used for induction and maintenance of anesthesia. Propofol has less negative inotropic action compared with thiopental, but it is a powerful peripheral vasodilator, and hypotension is a common problem. The drug is designed as a complete anesthetic, but it does not have powerful analgesic effects, and for painful operations it should be used with narcotics. Propofol has been approved for children younger than 3 years, but there is little experience with the drug in premature infants. Ketamine, a phencyclidine derivative, provides good hypnosis and amnesia and excellent analgesia. It is used rarely in adults and older children because it can cause a dissociative state with confusion, hallucinations, and other severe psychological side effects. Ketamine stimulates the sympathetic nervous system and causes minimal respiratory and cardiovascular depression. Blood pressure may increase, and increased intracranial pressure is a concern in infants with hydrocephalus or those at risk for intraventricular hemorrhage. Ketamine can be useful in breaking hypercyanotic spells in an infant with congenital heart disease and right-to-left shunt because it anesthetizes and increases systemic vascular resistance. Benzodiazepines are agents that produce sedation, anxiolysis, and amnesia, but little analgesia. They are incomplete anesthetic agents, although in adults they have been very useful in combination with an opioid. Midazolam is a very short-acting benzodiazepine, and it has been the most commonly used in anesthesia. Metabolism is almost entirely hepatic, and it should be expected that duration would be prolonged by immature hepatic function in a preterm neonate. In high doses, it can cause respiratory depression, although this is more common in conjunction with opioids. In the two studies analyzed, infants treated with midazolam were more sedated (as judged by varying scoring systems) compared with infants treated with placebo. The incidence of poor neurologic outcome was higher in the midazolam group, which at least raises questions as to the safety of midazolam infusion in these infants. Clearance is lowest in the most premature infants, and it increases with gestational age and with age after birth, probably reflecting increasing hepatic maturation. Volume of distribution of fentanyl also seems to vary depending on gestational age and disease state. Neonates with increased intra-abdominal pressure seem to have slower clearance of fentanyl. Slower clearance is likely a result of decreased hepatic blood flow resulting from the increased intra-abdominal pressure. There is a fairly wide therapeutic range, and even with high doses, hemodynamic stability is maintained. All narcotics are respiratory depressants, however, and with higher doses of fentanyl, prolonged respiratory depression occurs, necessitating postoperative assisted ventilation. Fentanyl in combination with a muscle relaxant has become the standard for anesthesia in premature neonates. Although fentanyl is a potent analgesic, it is not a complete anesthetic, and occasionally in adults, awareness has occurred with high-dose fentanyl alone. In the past, it was suggested that this was of minimal importance because neonates are not "aware," especially if pain was adequately treated. This belief is less well accepted today, and benzodiazepines or inhalational agents such as isoflurane are more commonly added to fentanyl anesthesia. Other synthetic narcotics, such as alfentanil and sufentanil, rarely have been used in neonates. In adults, alfentanil is less potent than fentanyl, but it has a shorter half-life, whereas sufentanil is more potent than fentanyl. Pharmacokinetics in infants is probably similar to fentanyl, and there does not seem to be any significant advantage compared with fentanyl. Remifentanil is a newer opioid whose duration of action is terminated by hydrolysis by tissue esterases. Consequently, remifentanil does not accumulate or have prolonged duration of action. Duration of action is very short, and it may be of use for procedural analgesia with little persistent pain. Duration can be extended by using a continuous infusion, but this can be associated with opioid-induced tolerance and hyperalgesia. Morphine is less potent than fentanyl, but it has a longer duration of action and is more commonly used for postoperative pain. In contrast to fentanyl, morphine causes histamine release, which limits its use as an anesthetic agent, although it is well accepted for analgesia, postoperative pain, and overall sedation. Morphine distribution in neonates has been well studied and is very predictable, although required target concentrations in neonates are still uncertain. As an aside, pre-emptive morphine administration for the stress of assisted ventilation in preterm neonates does not improve short-term outcome and may have negative developmental effects,1 although use for postsurgical pain is well established. Succinylcholine chloride is the only depolarizing agent used at present, and it remains the standard for rapid onset and rapid disappearance. Given the limited reserve and rapid desaturation in infants, the difficult airway problem is probably better handled with awake intubation, so that spontaneous ventilation can be maintained. Succinylcholine is not routinely used in children because of several rare but serious adverse reactions. In patients with myopathies or neurologic diseases, succinylcholine can cause overwhelming hyperkalemia, muscle necrosis, and cardiac arrest that is refractory to resuscitation. Bradycardia also occasionally occurs during intubation in infants with succinylcholine. For this reason, some anesthesiologists routinely administer atropine during a rapid-sequence intubation. Despite these reactions, succinylcholine at this point remains the choice for rapidsequence intubation. Nondepolarizing relaxants competitively inhibit acetylcholine at the neuromuscular junction. Pancuronium bromide is a long-acting relaxant, and it is probably the most commonly used relaxant in neonates when early extubation is not a problem. Vecuronium bromide is an intermediate-acting relaxant occasionally used in neonates. It has little effect on the cardiac system, although it may cause bradycardia in combination with narcotics. Cisatracurium besylate undergoes spontaneous degradation by a chemical process (Hofmann elimination), and duration is not affected by liver or kidney function. Atracurium, its parent compound, is rarely used today because it causes histamine release. Rocuronium bromide is an agent with a rapid onset of action that can be used in place of succinylcholine for rapid sequence. Duration of action is dose dependent and significantly longer than succinylcholine. Rapacuronium bromide also has a fast onset, but there is little information regarding use in neonates. Most relaxants probably have a prolonged duration of action in premature neonates, and frequency of dosing should be determined using a nerve stimulator to measure response to four spaced stimuli (train-of-four response). Induction of General Anesthesia Most sick infants have intravenous access, and an intravenous induction can be performed. Premedication rarely is given to neonates, although some anesthesiologists recommend atropine before laryngoscopy and intubation. Healthier infants without intravenous access can undergo mask induction, typically with 50% nitrous oxide and sevoflurane, after which intravenous access is rapidly obtained. Infants with a full stomach, most commonly infants with intra-abdominal disease, must have an intravenous rapid-sequence induction or an awake intubation. Thiopental and succinylcholine, with or without atropine, are rapidly pushed while an assistant performs the Sellick maneuver-pressure applied to the cricoid cartilage to prevent regurgitation of gastric contents. Positive pressure ventilation is not performed, and the infant is intubated expertly as soon as conditions are appropriate, usually after 45 to 90 seconds. There is little room for error with rapid sequence, and it should be performed only by individuals with significant expertise. Awake intubation with continued spontaneous ventilation is an alternative, and it may be most appropriate for infants with difficult airways, such as in Pierre Robin and Goldenhar syndromes. Minimal sedation can be given, but protective airway reflexes should not be obtunded. When the airway is secured, induction can continue by intravenous or inhalational route. Management of the difficult airway requires careful planning and the availability of additional "trained hands. Many infants, especially if they are hypoalbuminemic, should receive some replacement as colloid, usually 5% albumin. In the sickest neonates, transfusion with packed red blood cells, fresh frozen plasma, and platelets may be required. Use of oxygen has been discussed; if controlled ventilation is employed, care should be taken to avoid hyperventilation and subsequent hypocapnia. Using the ventilators on current anesthesia machines, it is easy to deliver excessive tidal volumes. Hypocapnia causes marked decreases in cerebral blood flow, which can easily be detected using cerebral oximetry employing near-infrared spectroscopy. Immaturity of drug clearance systems also prolongs recovery from the effects of most anesthetic agents in these infants.

Importantly treatment plan template compazine 5mg with visa, the women affected by these infections often have other risk factors for preterm birth treatment herniated disc buy generic compazine 5mg on-line. Consequently medicine venlafaxine cheapest generic compazine uk, only about 15% to 20% of patients at risk for preterm birth are true candidates for treatment medicine vs surgery order discount compazine. A significant volume of research has focused on predicting preterm birth in this cohort of patients medicine 3 times a day cheap 5mg compazine otc. Three main categories of risk factors are explored in the following paragraphs: classic predictors medicine used to treat bv trusted 5mg compazine, biochemical predictors, and ultrasound predictors. An association has been noted between the reported presence of contractions and preterm delivery. Beginning in the early 1980s, attempts were made to combine these various factors into a risk scoring system to determine which patients were at jeopardy for preterm delivery. Creasy and co-workers combined socioeconomic factors such as age, height, weight, previous medical history, smoking, work habits, and aspects of the current pregnancy into a risk scoring system. The initial study held promise, with a positive predictive value of 38%, but subsequent studies had much lower positive predictive values in the range of 18% to 22%. One of the limitations of the Creasy risk scoring system is the emphasis placed on previous preterm deliveries, a factor which by itself elevates a patient into a high-risk category. A total score of greater than 10 places the patient at high risk for spontaneous preterm delivery. Perhaps one of the most important biochemical markers identified to date is fetal fibronectin. Clinically, it serves as a prototypic example of a marker of choriodecidual disruption. Fetal fibronectin is usually absent from cervicovaginal secretions starting from the 20th week of gestation until near term. Detection of elevated cervicovaginal levels of fetal fibronectin has therefore been strongly associated with an increased risk for preterm delivery in high-risk patients. For example, Abbott and colleagues evaluated women with preterm labor symptoms, demonstrating an increasing positive predictive value for preterm birth of 19%, 32%, 61%, and 75% with increasing fetal fibronectin thresholds of 10 ng/mL, 50 ng/mL, 200 ng/mL, and 500 ng/mL respectively. Clinically, most experts rely primarily on the negative predictive value of fetal fibronectin, using negative results to justify management of women in an ambulatory fashion, thereby limiting inpatient hospitalization to only women at the highest risk for preterm birth. Estriol is another potential biochemical marker that may be of use in predicting preterm delivery. Levels of this hormone rise throughout pregnancy, with a characteristic exponential increase 2 to 4 weeks before the spontaneous onset of labor at term. Interestingly, patients undergoing induction of labor at term fail to demonstrate this increase in estriol, indicating that it plays a role in the onset of spontaneous labor. This finding has led to the theory that salivary estriol levels may be used to identify patients at risk for preterm delivery. As with many of the other markers, no reduction in the preterm birth rate has been demonstrated with the use of these assays, but they may play a role in limiting hospitalization of women who are ultimately unlikely to deliver prematurely. Each of these markers has been shown to have a modest correlation with spontaneous preterm delivery. This peptide appears to play a role in the initiation of parturition, with elevated levels noted weeks before the onset of preterm labor. Serum levels of these collagenases remain relatively constant until the onset of labor, when a marked increase occurs. This increase appears to be exaggerated in women who deliver prematurely, with an up to eightfold greater elevation in preterm births. In addition to the collagenases, the metalloproteinases and their inhibitors have received increasing interest in regard to their role in predicting preterm birth. The activity of granulocyte elastase has been shown to be increased in the cervix in both term and preterm labor, suggesting that it may be involved in cervical ripening and degradation of fetal membranes. Given the association of occult upper genital tract infection with early spontaneous preterm birth, a variety of serum, amniotic fluid, and cervicovaginal inflammatory markers has also been evaluated as potential markers for the prediction of spontaneous preterm delivery. To safely implement the use of these biochemical markers clinically, tests with improved sensitivity and specificity are needed. Of particular interest is the potential for a test combining a number of these assays. For example, Goldenberg and co-workers demonstrated that the use of a serum multiple marker test may enhance the predictive value of the presently available serologic markers for spontaneous preterm birth. Detection of these changes previously involved digital examination only, a test that is problematic because of such possible factors as the introduction of infection, interobserver differences, and an inability to evaluate the internal cervical os when the external os is closed. Ultrasonography therefore has several potential benefits, allowing for a more objective approach to examination of the cervix with visualization of changes earlier in the process of parturition. Several studies have compared digital examination with ultrasonographic assessment of the cervix. For example, Sonek and colleagues assessed patients at risk of preterm labor, reporting that digital examination tended to underestimate cervical length by about 1 to 1. Transabdominal ultrasound is technically more difficult because the distance between the transducer and the cervix is relatively long, particularly in obese patients. Transabdominal assessment of cervical length and internal os dilation may also be affected by bladder filling and emptying. Finally, fetal parts can cause acoustic shadowing of the cervix when looking abdominally. Transperineal ultrasonography is also effective in the assessment of cervical length, revealing findings that correlate well to those obtained via digital cervical examination and/or transvaginal imaging. In a study by Smith and colleagues, low-risk patients were observed serially via transvaginal ultrasonography, showing that the average cervical length of 37 mm remained stable between 10 and 30 weeks of gestation and then began to decrease slightly after week 32. Iams and colleagues, in a large multicenter trial, provided the clearest insights into the relationship between cervical length and spontaneous preterm delivery. An inverse relationship between cervical length and the rate of preterm delivery was noted in this study. The investigators concluded that the risk of spontaneous preterm birth is increased in women who are found to have a short cervix by transvaginal ultrasonography during pregnancy. Andrews and associates further evaluated the use of cervical ultrasonography to determine whether early cervical changes may predict spontaneous preterm delivery. It should also be noted that, in contrast to singleton pregnancies, cervical lengths differ significantly in higherorder gestations, probably reflecting a greater risk for subsequent preterm delivery. For example, dilation of greater than 5 to 7 mm has been shown to carry a sensitivity of 70% and a positive predictive value of 33. Parulekar and associates studied a cohort of patients with a reported history of cervical incompetence. In nearly 30% of these patients, dynamic findings were noted in which the internal os changed from 0-mm dilation to 42-mm dilation with no alteration of cervical length. Ultrasound assessment of the cervix represents a relatively easy way to identify patients who may be at higher risk for spontaneous preterm delivery, but the positive predictive value of this test is relatively low, and universal screening of all pregnant women remains controversial. For example, Defranco and colleagues performed a systematic review of nine studies that included a combination of fetal fibronectin testing and cervical length measurement to evaluate women with preterm labor symptoms. Care for these women should also involve accurate ultrasound dating, consideration of progesterone therapy beginning at 16 to 20 weeks of gestation, and close surveillance during the pregnancy for evolving findings. Programs attempting to decrease the rate of preterm delivery now use three main approaches: (1) education and surveillance programs, (2) serial cervical assessment, and (3) supplementation with progestins. Education and surveillance programs train women to recognize the symptoms of preterm labor. In the past, many of these programs also employed home uterine monitoring in an attempt to decrease preterm birth rates, but this intervention has since fallen out of favor. One of the largest intervention studies was conducted by Papiernik and co-workers in France from 1971 to 1982. These findings are hard to interpret because the investigation was not a controlled trial, such that changes in antenatal care during that decade make it difficult to assume that the improvement was due solely to the educational program. In subsequent studies modeled after the Papiernik design, no statistically significant differences were identified. Several theories may explain why these studies have failed to demonstrate significant improvements in the rates of preterm birth. First of all, the level of education and supervision may not have been adequate for the patient population under evaluation. The highest incidence of preterm delivery tends to consist of a population of lower socioeconomic status, in which education and surveillance may be more difficult to achieve. More importantly, early symptoms of premature labor are often subtle and varied, with diagnostic sensitivity less than 50%. For example, women often do not perceive contractions until labor is relatively advanced. Home uterine activity monitoring was therefore proposed as a potential solution to this problem. Katz and associates were the first to study home uterine monitoring performed intermittently (1 to 2 hours per day), with the data transmitted by telephone to a medical center for interpretation. Retrospective analysis showed that women with more than four contractions per hour had a higher risk of preterm labor, with a sensitivity of 57% to 80% and a positive predictive value of 72%. Katz and colleagues then conducted a prospective randomized trial in which the treatment group was monitored at home from 24 to 36 weeks of gestation with preterm labor education and daily nursing support provided via telephone. Outcomes were then compared with women enrolled in the control group, who experienced routine antenatal care, and women in the home uterine monitoring group were found to have a significant increase in the duration of pregnancy. Criticism of this trial primarily revolves around the role played by overdiagnosis of preterm labor and nursing support. For example, it is possible that the nursing calls, rather than the uterine monitoring, resulted in early diagnosis of preterm labor. Only one study has completely separated the issue of home monitoring from that of nursing support. Mou and associates randomly assigned high-risk patients to monitoring or no monitoring such that the monitored group phoned in their data but received no medical advice. Several subsequent trials then compared nursing support to home uterine monitoring. A study by Dyson and co-workers concluded that daily nursing support was more effective than home monitoring in women with a twin gestation, although this conclusion may be invalid because the same nursing team was involved in both groups. The women in the arms that included daily contact with a nurse with or without home uterine monitoring, though, had more visits to the hospital and were more frequently treated with prophylactic medications. Although some of these earlier and smaller trials of home uterine activity monitoring demonstrated a significant decrease in preterm births among enrolled subjects, subsequent studies have not shown a benefit. The use of home uterine activity monitoring is a cautionary tale, because it was introduced into clinical practice and heavily marketed without benefit of scientific rigor. In fact, it may be harmful in that monitoring may lead to unnecessary hospital admissions and/or intervention such as tocolysis or cerclage placement. Experts have therefore concluded that home uterine activity monitoring has no clinical value at this time and should not be used to manage patients outside of a randomized, controlled clinical trial. Manuck and colleagues evaluated the rates of recurrent spontaneous preterm births in women assigned either to receive care in a consultative preterm birth prevention clinic (70 patients) or a routine prenatal care clinic (153 patients). These findings suggest that preterm birth prevention clinics may play a role in the care of high-risk women. Treatment One of the primary obstacles encountered when deciding on the optimal therapeutic intervention to prevent preterm delivery is the difficulty in accurately distinguishing between preterm labor and preterm contractions. Another issue that must be addressed is how aggressively one should pursue treatment. However, beyond this gestational age, when neonatal morbidity and mortality rates begin to approach those of term infants, maternal treatment becomes more controversial. Many of the interventions discussed in this section have the potential for significant maternal and fetal side effects, and the risks of these adverse events must be weighed against the benefits of treatment in each individual patient. Therapeutic interventions employed in the setting of preterm labor have the following purposes: (1) to prevent premature labor, (2) to control contractions when they do occur and delay the time from onset of contractions to the actual time of delivery, and (3) to optimize fetal status and maturation before preterm delivery. Most efforts to prevent preterm labor have not proven to be effective, and, equally frustrating, most efforts at arresting preterm labor once started have also failed. Management has therefore focused more on preventing neonatal complications, including antenatal administration of corticosteroids for enhancement of fetal lung maturity and intrapartum antibiotics for prevention of group B streptococcal neonatal sepsis. Ensuring delivery in a medical center with an experienced resuscitation team and the availability of a high-quality newborn intensive care unit also helps to optimize neonatal outcomes. Prescribing bed rest is inconsistent with the ethical principles of autonomy, beneficence, and justice. At least two theories exist in regard to the mechanism of action behind hydration as a potentially effective treatment for preterm contractions. The first theory holds that hydration inhibits the release of antidiuretic hormone through the Gauer-Henry reflex. The second theory is based on the suggestion that patients with preterm labor are hypovolemic, a theory supported by the delay in delivery that may be seen when women with preterm contractions are treated with albumin in an effort to expand plasma volume. Despite these theories, few studies have prospectively evaluated the use of hydration in women with preterm contractions, and those that do exist actually suggest no benefit to this intervention. For example, in one trial, the combination of bed rest and aggressive hydration was found to be no more effective than bed rest alone in stopping contractions. When the contractions actually did stop, patients in both groups remained at equally high risk for subsequent preterm birth. Another study by Guinn and colleagues reported similar findings in a prospective, randomized trial of 179 women with preterm contractions. No significant differences were noted among the three groups in regard to the interval between intervention and delivery or the incidence of preterm birth, suggesting that intravenous hydration offers no clinical benefit. Sedation is another strategy that has been used to differentiate between preterm contractions and true preterm labor. As with hydration, limited data document the efficacy of sedation in this clinical setting. Helfgott and associates performed a prospective comparative study of 119 women with preterm labor who were randomly assigned to treatment with hydration and sedation or to the control treatment of bed rest alone.

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