By P. Ur-Gosh. Neumann College. 2019.
Activation of dopamine receptors dilates renal blood vessels sildalis 120mg, thereby increasing renal blood flow and urine output 120mg sildalis. Activation of alpha receptors increases vascular1 resistance (afterload) and can thereby reduce cardiac output 120 mg sildalis. Dopamine is employed as a short-term rescue measure for patients with severe sildalis 120 mg, acute cardiac failure . Dobutamine Dobutamine is a synthetic catecholamine that causes selective activation of beta -adrenergic receptors . By doing so , the drug can increase myocardial1 contractility and can thereby improve cardiac performance . In contrast to dopamine , dobutamine does not activate alpha receptors and therefore does1 not increase vascular resistance . Phosphodiesterase Inhibitors Milrinone Milrinone has been called an inodilator because it increases myocardial contractility and promotes vasodilation. Use should be reserved for patients with severe reduction in cardiac output resulting in decreased organ perfusion because ionotropes can induce dysrhythmias and cause myocardial ischemia from increased metabolic demand. Worse yet, although nesiritide offered no benefit, it nearly doubled the incidence of hypotension. These results led the authors to conclude that “Nesiritide cannot be recommended for routine use in the broad population of patients with heart failure. However, whereas nitroglycerin acts primarily on veins, nesiritide dilates arterioles as well. Also, by dilating afferent renal arterioles, nesiritide increases glomerular filtration rate, and thereby increases excretion of sodium and water. Nesiritide is eliminated by three mechanisms: (1) proteolytic cleavage by endopeptidases present on the luminal surface of blood vessels; (2) binding to clearance receptors on the surface of cells, followed by cellular uptake and proteolytic cleavage; and (3) renal filtration. The risk for hypotension is increased by high doses of nesiritide and by concurrent use of angiotensin-converting enzyme inhibitors and other vasodilators. In addition to causing hypotension, nesiritide can cause ventricular tachycardia, headache, back pain, dizziness, and nausea. An analysis of several clinical trials suggested that nesiritide might cause renal damage. Dosages are as follows: • Adults and children 13 years and older who weigh more than 50 kg—1000 mg every 6 hours or 650 mg every 4 hours as needed. The first dose—150 mg/kg (in 200 mL of 5% dextrose)—is infused over 15 minutes to 1 hour. And the third dose—100 mg/kg (in 1000 mL of 5% dextrose)—is infused over 16 hours. Fortunately, these reactions tend to be mild and self-limited and can be minimized by infusing the initial dose slowly (over a 1-hour interval). The usual dose for adults is 4 to 10 mg (diluted in 4–5 mL of sterile water for injection). Epidural and Intrathecal When morphine is employed for spinal analgesia, epidural injection is preferred to intrathecal. With either route, onset of analgesia is rapid and the duration prolonged (up to 24 hours). The most troubling side effects are delayed respiratory depression and delayed cardiac depression. The extended-release liposomal formulation [DepoDur], used only for postsurgical pain, is intended for epidural use only. Inadvertent intrathecal and subarachnoid administration has been associated with profound and prolonged respiratory depression, which can be managed with a naloxone infusion. Dosing is highly individualized and must account for age, body mass, physical status, history of opioid use, risk factors for respiratory depression, and medications to be coadministered before and during surgery. The drug is well suited for these applications, owing to its rapid onset and short duration. In addition, fentanyl can cause muscle rigidity, which can interfere with induction of anesthesia. Nalbuphine Nalbuphine is an agonist at kappa receptors and an antagonist at mu receptors. As a result, the maximal pain relief that can be produced with nalbuphine is much lower than with morphine. Symptoms of abstinence are less intense than with morphine but more intense than with pentazocine. When used during labor and delivery, nalbuphine has caused serious adverse effects, including bradycardia in the fetus and apnea, cyanosis, and hypotonia in the neonate. Nalbuphine has a low abuse potential and is not regulated under the Controlled Substances Act. Like pentazocine, nalbuphine will precipitate a withdrawal reaction if administered to an individual physically dependent on a pure opioid agonist. This control limits the total dose that can be administered each hour, thereby minimizing the risk for overdose. This interval, referred to as the “lock-out” or “delay” interval, prevents the patient from administering a second dose before the first has had time to produce its full effect. The size of the bolus should be increased if analgesia is inadequate and decreased if excessive sedation occurs. The size of the bolus dose is usually increased during sleeping hours, thereby promoting rest by prolonging the interval between doses. Comparison of Patient-Controlled Analgesia and Traditional Intramuscular Therapy The objective of therapy with analgesics is to provide comfort while minimizing sedation and other side effects, especially respiratory depression. This objective is best achieved by maintaining plasma levels of opioids that have minimal fluctuations. In this manner, side effects from excessively high levels can be avoided, as can the return of severe pain when levels dip too low. Shortly after the injection, plasma levels may rise very high, causing excessive sedation and possibly respiratory depression. Late in the dosing interval, pain may return as plasma levels drop to their lowest point. Because the patient can self- administer a parenteral dose of opioid as soon as pain begins to return, there is minimal delay between detection of pain and restoration of an adequate drug level. With traditional therapy, the patient must wait for the nurse to respond to a request for more drug; this delay allows pain to grow more intense. Families should be informed that activating the device for the patient while he or she is sleeping can lead to drug overdose. Patients should be informed that there is a time lag (about 10 minutes) between activation of the device and production of maximal analgesia. To reduce discomfort associated with physical therapy, changing of dressings, ambulation, and other potentially painful activities, patients should be taught to activate the pump prophylactically (e. Using Opioids for Specific Kinds of Pain Postoperative Pain Opioid analgesics offer several benefits to the postoperative patient. In addition, by reducing painful sensation, opioids can facilitate early movement and intentional cough. In patients who have undergone thoracic surgery, opioids permit chest movement that would otherwise be too uncomfortable for adequate ventilation. By promoting ventilation, opioids can reduce the risk for hypoxia and pneumonitis. In addition, analgesia may delay diagnosis of postoperative complications—because pain will not be present to signal them. Obstetric Analgesia When administered to relieve pain during delivery, opioids such as morphine or meperidine may depress fetal respiration and uterine contractions when administered parenterally. Although these drugs are still used for relief of labor pain, regional and epidural modes of analgesia are often favored for pain relief in childbirth. For patients who are hesitant to use these more invasive methods, providers are employing newer opioid medications. Fentanyl, sufentanil, alfentanil, and remifentanil have a short duration of action and should not produce significant neonatal depression. The mixed opioid agonist-antagonists— nalbuphine, butorphanol, pentazocine, and buprenorphine—offer increased pain relief without causing further respiratory depression in higher doses. Even if these newer medications are used, however, respiration in the neonate should be monitored closely after delivery. Dosage should be titrated with care; the objective is to achieve adequate ventilation and alertness without reversing opioid actions to the point of unmasking pain. Dosing is repeated at 2- to 3-minute intervals until a satisfactory response has been achieved. Additional doses may be needed at 1- to 2-hour intervals for up to 72 hours, depending on the duration of the offending opioid. Alvimopan Alvimopan [Entereg] is a selective, peripherally acting mu opioid antagonist developed to counteract the adverse effects of opioids on bowel function. At therapeutic doses, alvimopan does not reduce opioid-mediated analgesia, in part because of limited ability to cross the blood-brain barrier. In contrast to methylnaltrexone, which is approved for long-term therapy of constipation in patients taking opioids for chronic pain, alvimopan is approved only for short- term therapy of opioid-induced ileus after partial small or large bowel resection with primary anastomosis. The goal is to accelerate time to recovery of upper and lower bowel function, which can be impaired by opioids used for analgesia during and after surgery. The drug may be used alone for mild to moderate pain or combined with an opioid for moderate to severe pain. Caldolor is supplied as a concentrated solution (100 mg/mL) that must be diluted (to 4 mg/mL or less) before use. For patients with pain, the usual dosage is 400 to 800 mg every 6 hours as needed. For patients with fever, treatment consists of an initial 400-mg dose, followed by either (1) 400 mg every 4 to 6 hours or (2) 100 to 200 mg every 4 hours as needed. Ketorolac Parenteral therapy with ketorolac can be accomplished with one injection or with several. In all cases, the smaller dosage option is employed for patients older than 65 years, patients with impaired kidney function, and patients who weigh less than 50 kg (110 pounds). Peptic Ulcer Disease Antagonists Cimetidine Parenteral cimetidine (discussed in Chapter 62) is reserved for patients with hypersecretory conditions (e. For children aged 1 year to 17 years, the daily dose is either 10 mg (for those who weigh less than 55 kg) or 20 mg (for those who weigh 55 kg or more). Our management is based on the latest 2016 clinical guidelines released by the American Epilepsy Society. The goals of treatment are to maintain ventilation, correct hypoglycemia and precipitating factors, and terminate the seizure as quickly as possible. After 30 minutes, continued seizure activity can cause permanent neurologic injury (cognitive impairment, memory loss, worsening of the underlying seizure disorder) and even death. Clinical guidelines propose a stabilization phase followed by three therapy phases. All of these drugs can terminate seizures quickly: however, lorazepam is generally preferred for its longer duration of action. The patient may present with either symptoms of angina at rest, new- onset exertional angina, or intensification of existing angina. The risk for dying is greatest initially and then declines to baseline in about 2 months. According to the guideline, the treatment strategy is to maintain oxygen supply and decrease oxygen demand. Acute management consists of antiischemic therapy combined with antiplatelet and anticoagulation therapy. If beta blockers are contraindicated, substitute a nondihydropyridine calcium channel blocker (verapamil or diltiazem). Angiotensin receptor blockers are a reasonable alternative in patients who have intolerance to angiotensin-converting enzyme inhibitors. The infusion rate is 5 mcg/min initially and then is increased gradually until an adequate response has been achieved. The Health Products and Food Branch within Health Canada is responsible for ensuring that health products and foods approved for sale to Canadians are safe and of high quality. The Biologics & Genetic Therapies Directorate regulates biologic drugs (drugs derived from living sources) and radiopharmaceuticals. Examples of biologic products are insulin analogues, blood products, and vaccines. The Natural and Non-prescription Health Products Directorate is the regulating authority for natural health products for sale in Canada. The Food and Drug Act (1927), accompanied by the Food and Drug Regulations (1953, 1954, 1979), reviews the safety and efficacy of drugs before they are marketed, and the legislation determines whether the medicine is classified as prescription or nonprescription status. The Act controls the requirements for good manufacturing practices, labeling, distribution, and sale, including advertising of the drug. They also prescribe the standards of composition, strength, potency, purity, and quality of drugs in Canada. Prescription Drugs (Schedule F) All drugs that require a prescription, except for narcotics and controlled substances, are listed in Schedule F of the Food and Drug Regulations. Prescriptions for Schedule F medications may be written, including facsimiles and electronic prescriptions (depending on the province), or transmitted verbally (i. The Controlled Drugs and Substances Act (1997) establishes the requirements for the control and sale of narcotics, controlled drugs, and substances of abuse in Canada. The Controlled Drugs and Substances Act lists eight schedules of controlled substances. Assignment to a schedule is based on potential for abuse and the ease with which illicit substances can be manufactured in illegal laboratories. The degree of control, the conditions of record keeping, and other regulations depend on the specific schedule.
Hispanic youth rates fall between sildalis 120mg, except for 12th grade Hispanics 120mg sildalis, who report the highest rate of crack cocaine sildalis 120 mg, injected heroin 120 mg sildalis, and crystal methamphetamine use . Numbers are likely underestimated , though , because the survey only targets those who are in school , and excludes drop-outs , the homeless and incarcerated; illicit drug use is typically higher in these three groups . Substance use disorder combines their previous diagnostic criteria, strengthening their ability to classify substance use and abuse onto a scale. Two or three symptoms indicate a mild substance use disorder; four or five a moder- ate disorder; and six or more a severe disorder. Recurrent substance use resulting in a failure to fulfill major role obligations (poor school performance, suspensions, expulsions). Recurrent substance use in situations in which it is physically hazardous (driv- ing an automobile). Continued substance use despite having persistent or recurrent social or inter- personal problems. Tolerance to the substance (a need for markedly increased amounts of the sub- stance to achieve intoxication and/or markedly diminished effect with contin- ued use of the same amount of the substance). Withdrawal from the substance (the characteristic withdrawal syndrome for the substance, or the same [or a closely related] substance is taken to relieve or avoid withdrawal symptoms). The substance is often taken in larger amounts or over a longer period than was intended. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects. Important social or recreational activities are given up or reduced because of substance use. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance. As yet, criteria for diagnostic use have not been developed for adolescents, though most clinicians will refer them for substance abuse treatment based on the previously listed points. Such binge-drinking adolescents are at a higher risk of alcohol poisoning (suppression of the gag reflex and respiratory drive), high-risk sexual behaviors, academic problems, and more injuries than nonbinge drinking peers. Alcohol use is the primary contributor to the lead- ing causes of death among adolescents (motor vehicle accidents, homicide, suicide). Acute ingestion can result in erosive gastritis, manifested by epigastric pain, anorexia, vomiting, and hematochezia and pancreatitis (mid-epigastric pain and vomiting). Alcohol overdose should be suspected in an adolescent who is disoriented, lethargic, comatose, or who smells of alcohol. In alcohol poisoning, if obtundation appears out of proportion to the reported blood alcohol level, head trauma, hypoglycemia, or other drug ingestion, it should be considered as a possible confounding factor. Unwanted side effects include decreased reaction time, impaired attention and con- centration, and short-term memory loss. Physiologic signs of cannabis intoxication include tachycardia, increased blood pressure, increased respiratory rate, conjuncti- val injection, dry mouth, and increased appetite. Chronic use by males results in dose-related suppression of plasma testosterone levels and spermatogenesis. Cocaine and Amphetamines Cocaine and amphetamines are central nervous system stimulants that increase dopa- mine levels by preventing reuptake. Cocaine may elicit euphoria, increased motor activity, decreased fatigability, and mental alertness. Chronic use of intranasal cocaine is associated with loss of smell, nosebleeds, and chronic rhinorrhea. When mixed with alcohol, cocaine is metabolized by the liver to produce cocaethylene, a substance that is significantly more cardio- and hepatotoxic than alcohol or cocaine alone. These medications have become a significant drug of abuse among children and adolescents. Illicit metham- phetamine is produced in illegal laboratories and is popular among adolescents and young adults because of its potency and ease of absorption. Amphetamines and cocaine are associated with increased physical activity, rapid and/or irregular heart rate, increased blood pressure, and decreased appetite. Binge effects result in the development of psychotic ideation with the potential for sudden violence. Acute agitation and delusional behaviors can be treated with haloperidol and may be diminished by administering a sedating dose of lorazepam or diaz- epam. Marked reactive hypertension or dysrhythmia may need treatment with a cardiovascular agent (β-blocker) until the intoxication resolves. As in teens with other drug use, com- prehensive cognitive-behavioral interventions have been shown to be an effective treatment modality. Sympatho- mimetic effects include mydriasis, tachycardia, hypertension, and hyperreflexia. Overdoses have been associated with respiratory arrest, severe hyperthermia, and coagulopathy. Somatic symptoms of ingestion include nausea, jaw clenching, teeth grinding (bruxism), and blurred vision. Reported impairments include memory loss, diminished learning ability, sleep disturbances, and depression. Common products include volatile solvents (paint thinners, glue), aerosols (spray paint, hair spray), and gases (propane tanks, lighter fluid). Paint “huffers” often present with residual perioral or fingertip paint from inhalation. Because of the increased solvent content in metallic-colored paints, gold and silver spray paints are particularly popular. Initial stages of acute inhalant use are characterized by eupho- ria, excitation, exhilaration, dizziness, hallucinations, excess salivation, sneezing, flushed skin, and bizarre behavior. More concerning signs of inhalant intoxication are disorientation, double vision, nystagmus, bizarre dreams, epileptiform activity, arrhythmias, and unconsciousness. Chronic use causes difficulty coordinating movement, gait disorders, muscle tremors, and spasticity due to neurotoxic effects of inhalants, hypoxia, or both. Other toxicity includes pulmonary hypertension, restrictive lung defects or reduced diffusion capacity, hematuria, tubular acidosis, and possibly cerebral and cerebellar atrophy. Treatment is supportive and directed toward control of dysrhythmias and stabi- lization of respirations and circulation. Bath Salts “Bath salts” are newly popular drugs that act as a central nervous system stimulant by inhibiting norepinephrine-dopaminergic reuptake. Legal until early 2012, “bath salts” con- sumption and distribution was widespread and difficult to follow. Common symp- toms include euphoria, dilated pupils, loss of inhibition, involuntary muscle move- ment, tachycardia, and hypertension. Thus, early diagnosis and intervention at routine health screenings is an important component of the well-child examination. In addition, a family history of drug addiction or abuse should raise the level of concern about potential drug abuse. A significant change in school performance or other daily behaviors is noted, and frequent or serious accidents occur (atypical motor vehicular accidents). Screening and diagnostic testing in an older, competent adolescent may be carried out, with few exceptions, only with the patient’s consent. Parental permission is not sufficient for involuntary screening in these patients. Consent may be waived when the patient’s competency is questionable or when findings from the interview and physical examination strongly suggest the patient is at high risk for serious harm from substance use. Staging substance abuse provides the clinician with a means of monitoring progress and providing an objective means of conveying treatment goals (Table 49–2). Group counseling, individualized counseling, and multifamily educational intervention have been found to be effective interventions for teens with substance use disorders. Outpatient management is often the first line of treatment for teens identified as meeting Stage 4 or Stage 5 criteria. Candidates for inpatient treatment have significant comorbid psychiatric illness; are experiencing withdrawal; have sui- cidal ideation, runaway behavior, behavior that threatens the lives of their family and/or friends; or have not responded to intensive outpatient treatment. Certain substances are commonly associated with specific comorbid psychiatric diagnoses: amphetamines with eating disorders; cocaine with depression; marijuana with amotivational syndrome; and alcohol use with affective disorder, anxiety disorder, and mania. Asthma (Case 20) can be triggered by any pulmonary irritant, tobacco being one of the most common. The younger child who is exposed to exogenous testosterone, such as accidental exposure to parental testosterone replacement, may have precocious puberty (Case 45) as a finding. Young infants who are born to or in homes with substance abus- ing caretakers are at higher risk of sudden infant death syndrome (Case 21) and child abuse (Case 38). Stage 2 Experimentation • May try various drugs, typically out of curiosity or to “fit in with friends. Drug Seeking • Multiple consequences and risk taking in order to obtain Preoccupation drugs or hide drug use. He is brought to the local emergency depart- ment, where he appears euphoric, emotionally labile, and a bit disoriented. On examination he is a healthy, athletic-appearing 17 year old with decreased extraocular range of motion and left eye visual acuity. Parents are unaware of drug use, but did note he has been acting “dazed and confused” at times, and that his hygiene has worsened over the past few months. Despite previous drug experimentation, his current neurologic symptoms and physical findings make drug use a less likely etiology. Previous criteria were combined for abuse and dependence, with the exception of “drug craving,” a new addition, and “problems with law enforcement,” eliminated due to cultural considerations. Management of the adolescent with substance use disorders and comorbid psychopathology. Committee on Substance Abuse, American Academy of Pediatrics; Council on School Health, American Academy of Pediatrics. Testing for drugs of abuse in children and adoles- cents: addendum—testing in schools and at home. The mother reports that because of lack of insurance she has not had a regular pediatrician for her children for the previous 8 years. She reports the girl to be in generally good health other than recurrent bouts of otitis media. The mother is concerned that she and her other two daughters began their growth spurts and their menstrual cycles by age 11 years, but this child “hasn’t got her period. On physi- cal examination, she is at the 5th percentile for height and the 90th percentile for weight. Select appropriate diagnostic tests and treatments for a patient with Turner syndrome. Considerations The patient has several of the common clinical abnormalities found in individuals with Turner syndrome. While no single, “classic” presentation of Turner syndrome is seen, girls often are diagnosed later in childhood due to short stature or primary amenorrhea. Findings that prompt earlier diagnosis include webbed neck, lymph- edema, cubitus valgus, and low posterior hairline. Mosaicism can be seen and can ame- liorate expression of some of the clinical findings. The prevalence of Turner syndrome is between 1 in 2000 to 5000 live female births. With high-resolution prenatal ultra- sound, a fetus with severe lymphedema or hydrops fetalis can be identified. Girls with Turner syndrome have a wide variety of clinical abnormalities that necessitate comprehensive care. When Turner syndrome is suspected, a karyotype is performed to confirm the diagnosis. If the diagnosis is suspected during a prena- tal ultrasound, chorionic villi sampling or amniocentesis can harvest fetal cells for karyotyping. Neonates with Turner syndrome are often noted to have lymphedema which creates swollen hands and feet. Other clinical features in the newborn period include webbed neck, low set ears, low hairline, broad chest with wide spaced nipples, drooping eyes, and a higher incidence of hip dysplasia. At the time of diagnosis, a team consisting of cardiology, genetics, and endocrinology is established to evaluate and manage the disorder. On physical examination, differences in upper and lower body pulse intensity or blood pressure differences are evaluated. Less commonly seen defects include aortic root dilation, bicuspid aortic valve, mitral valve prolapse, and hypoplastic left heart syn- drome. Overall, patients with monosomy X are more likely to have these structural abnormalities. Hypo- thyroidism and glucose intolerance are common; thyroid function tests and serum glucoses are tested routinely. Short stature is universally present; treatment by a pediatric endocrinologist with growth hormone is considered. Many girls with Turner syndrome (especially those with monosomy X) have absent pubertal devel- opment and have “streak” ovaries that do not ovulate. To promote the development of secondary sex characteristics (pubic hair, breast development), estrogens can be initiated in these girls early in their teen years. Mosaic Turner syndrome patients are more likely to have appropriate start of puberty and can become pregnant. Other ocular abnormalities include congenital glaucoma and anterior chamber deformities. Plastic surgery can be considered for girls for whom defects of the neck, face, and ears are particularly troublesome. Dental malocclusion is often seen and requires the services of a pediatric orthodontist. In addition, scoliosis, kyphosis, and lordosis are more commonly seen and are monitored by the primary care provider.
If the patient herself had a prior baby with Down syndrome 120 mg sildalis, the risk would be substantially increased sildalis 120mg, and genetic counseling with possible amniocentesis for karyot ype would be appropriate 120mg sildalis. Thus sildalis 120 mg, many practitioners will perform serial ultrasound exami- nations , monitor for these complications , and perform fetal antenatal testing such as biophysical profile t est ing . G en et ic cou n selin g is ap pr opr iat e wit h a fam ily h ist or y of p ossible h er it able syndromes . A glucose challenge t est would not be helpful in evaluat ing heri- table syndromes because it is used as a screen for gestational diabetes . Genetic counseling is recommended before a risky procedure , such as an amniocentesis, is performed because based on the family h ist ory, it may not be indicat ed in this situation. Lithium is associated with Epstein anomaly (a fetal heart malformation); Dilantin is associated with a fetal hydantoin syn- drome of intrauterine growth retardation, microcephaly, and facial defects. Antepartum care: preconception and prenatal care, genet ic evaluat ion and teratology, and antenatal fetal assessment. N oninvasive prenatal diagnosis of Down syndrome: current knowledge and novel insight s. She has a known twin pregnancy, and throughout the pregnancy, she had significant nausea and vomit- in g, b u t o the rwise h e r p re n a t a l co u rse h a s b e e n u n re m a rka b le. Se ria l u lt ra so u n d examinations have been performed showing concordant growth of the twins. Ultrasound examination reveals a twin pregnancy with a dividing membrane, and adequate amniotic fluid. Ar t i f i c ia l r u p t u r e o f m e m b r a n e s is u n d e rt a ke n t o a llo w fo r a fe t a l sca lp e le ct ro d e o f t win A. A m o d e ra t e a m o u n t of vaginal bleeding is noted after rupture of membranes. Twin A’s fetal heart rate tracing initially was in the 140 bpm baseline, and then increases to 170 bpm, and now has a sinusoidal appearance. Cause of this condition: The exact pat hophysiologic mechanism of vasa previa is not known, but it is associat ed wit h a velament ous cord insert ion (explained below), accessory placental lobes, and second trimester placenta previa. Next step: Stat cesarean and alert pediatricians for likelihood of anemia in twin A. Understand the implications of twin gestation for a pregnancy (both maternal and fet al effect s). Co n s i d e r a t i o n s This 31-year-old woman presents with a known twin gestation and ultrasound findings consistent with a vasa previa, where a fet al vessel overlies the internal cer- vical os. This p r esen t s a d an ger t o the fet u s wh en r u p t u r e of m em b r an es occu r s, as the fetus can rapidly exsanguinate. Prenat al diagnosis of this condition is of the utmost importance, as there is nearly a two-fold increased chance of survival with prenatal diagnosis; unfort unat ely, it is difficult t o diagnose prenat ally. T h e t win ges- tation has its own set of possible complications that must be considered. These include the increased risk of congenit al anomalies, pret erm labor, preeclampsia, postpartum hemorrhage, and maternal death. T his is a result of the increasing use of infertility treat ments, including ovulation induction and in vitro fertilization. T his dramat ic increase has created a new public healt h concern, as t win pregnancies are associat ed wit h a higher rate of preterm delivery and all of t he complicat ions associated wit h it. T h e ot h er complicat ion s of t win gest at ion include a h igh er rat e of congenit al malformations, a two-time increased risk of preeclampsia and postpartum hemor- rhage, and twin– twin transfusion (T T T ) syndrome. Monozygotic twins are formed when one egg is fertilized by one sperm followed by an error in cleavage; t he incidence is not relat ed to race, h eredit y, age, or parit y. The exact mechanism of monozygotic twinning is not known, but may be caused by a delay in normal event s, such as wh en tubal mot ilit y is decreased. Relat ive t o dizygot ic t wins, monozygotic twins are associated with a higher incidence of discordant growth and malformations, with monochorionic twins being associated with a much higher rate of spontaneous abortion. The incidence is influenced by race, heredit y, maternal age, parit y, and fert ilit y drugs. There is an increased incidence of a t win pregnancy when the mother is a dizygot ic t win. Clomiph en e in duces ovulation and promotes the maturation of multiple follicles, therefore increasing the number of eggs released during ovulation and available for fertilization. In vitro fer t ilizat ion involves the t ran sfer of t wo t o four embr yos t o the ut er u s. The bottom arrow points to yolk sac and the top arrow points to dividing membrane. H emody- namically, blood volume and stroke volume are increased more than in a singleton pregnancy. H owever, the red cell mass increases proportionately less, so there is great er ph ysiologic an emia. Blood pr essure at 20 weeks is u sually lower t h an in a singleton pregnancy, but is higher by delivery. Finally, there is a greater increase in size and weight of t he uterus, as might be expected. Maternal complications more common with multiple gestations include pre- eclampsia, gest at ional diabet es, anemia, deep venous t hrombosis, postpartum hem- orrhage, and the need for cesarean delivery. In T T T syndrome, one twin is the donor and the other the recipient such that one twin is larger with more amniotic fluid and the other twin smaller with oligohydramnios. Treatment includes laser ablation of the shared anastomotic ves- sels at special centers, or serial amniocentesis for decompression. W hen there is no dividing membrane between the twins, cord entanglement can occur, leading to a 50% perinatal mortality rate. Thus, an important part of the ultrasound evaluation of twin gestations is identification of a dividing membrane. When a multiple gestation is diagnosed, the patient should be followed in a high-risk clinic with serial ultrasound examinations for growth and comparison weight, and careful monit oring for t he above complicat ions. When the first twin is nonvertex, cesar ean d eliver y is u su ally p er for m ed. W h en the fir st t win is ver t ex, d eliver y of the nonvertex second twin is individualized. It is difficu lt t o id en - tify on vaginal examination, especially before membrane rupture, and ultrasound may give some hint. Currently, accepted risk factors are a bilobed, succenturiate- lobed, or low-lying placent a, mult ifet al pregnancy, and pregnancy result ing from in vit r o fer t iliz at ion. W om en wit h t h ese r isk fact or s or su ggest ive u lt r asou n d fin d in gs should have a color D oppler ult rasound. If vasa previa is ident ified, a planned cesar- ean delivery should t ake place before rupture of membranes, around 35 t o 36 weeks of gestation. Becau se fet al blood volu m e at t er m is on ly 250 t o 500 cc, it is n ot h ar d t o imag- ine t hat t he fetus may exsanguinate wit hin minutes of an umbilical vessel being torn. Fetal heart rate abnormalities such as tachycardia, recurrent decelerations, prolonged bradycardia, and a sinusoidal pattern can indicate serious fet al compro- mise and should prompt evaluation for its cause. If fetal bleeding is uncertain, the Apt test and Kleihauer– Betke test can be used to different iate fetal from maternal blood. Careful examinat ion of the membranes reveals that t h ere is a very t hin membrane bet ween t he t wo fetuses. Her ultrasound findings are as follows: Tw in A Tw in A Es t i m a t e d w e i g h t 500 g 1100 g Am n io t ic flu id 2 cm 26 cm Which of the following is the best next step for this patient? She has been followed in a high-risk obstetrics clinic with an uncomplicated pregnancy course. She arrives to the hospital labor and delivery unit at 30 weeks’ gestation with a blood pressure of 150/ 100 mm H g, and 2+ proteinuria. The ultrasound findings are consistent with monochorionic, diamniotic twins, since there is only a thin membrane between the two gestations. Since a dizygotic gestation always gives rise to a dichorionic diamniotic gestation, this patient must have a monozygotic pregnancy which split at 4 to 8 days after fer t ilizat ion. The large discrepancy of fetal weight and amniotic fluid volume between the two gestations is consistent with T T T syndrome. The best treatment is laser ablat ion of the sh ared vessels, but this procedure is only available at select centers. In T T T syndrome, one twin acts as the donor (smaller) and the other as the recipient (larger). This pat ient likely h as pu lmon ar y ed ema du e t o pr eeclampsia as well as the increased plasma volume due to mult iple gest at ions. The h igher t he number of pregnancies, the more the plasma volume, and greater the risk of pulmonary edema. T his pat ient should be placed on int ravenous furosemide t o decrease int ravascular volume, magnesium sulfat e for seizure prophylaxis, and plans made for delivery. The chest radiograph would be h elpful t o different iat e the t wo condit ions (infilt rat es wit h pulmo- nary edema, clear in pulmonary embolism). Tocolysis and corticosteroids would be useful in isolat ed pret erm labor, alt h ough many expert s avoid t h eir use in multiple gestations because of the risk of pulmonary edema. Mo n o z y g o t i c twins are associated with a higher rate of anomalies and maternal com- plications. Sh e d e n ie s a n y b list e rs, a n d h e r la st h e rp e t ic o u t b re a k wa s 4 m o n t h s ago. The vag in al flu id is co n sist e n t wit h ru p t u re of m e m b ran e s, sh owin g fe rn in g an d an alkalotic pH. Co n s i d e r a t i o n s The patient is in labor and has experienced rupture of membranes. Although she has no lesions visible and is taking acyclovir sup- pressive therapy, she complains of tingling of the perineal region. T hey are helpful in making the diagnosis during the prenatal course, when the patient may develop lesions and the diagnosis is in question. A met iculous in spect ion of the ext ernal gen it alia, vagina, cer vix (including by speculum examination), and perianal area should be undertaken for the typical herpetic lesions, such as vesicles or ulcers (Figure 9– 1). W hen there are no lesions or prodromal symptoms, the patient should be counseled that she is at low risk for viral shedding and likely has a small but possible risk of neo- natal herpes infection. N ewer medicat ions such as valacyclovir or famciclovir require less frequent dosing due t o t h eir increased bioavailabilit y, but are more expensive. The use of oral suppressive antiviral therapy at 36 weeks for women who have had a recurrence or first episode during pregnancy has been shown to decrease vir al sh ed d in g an d the fr equ en cy of ou t b r eaks at t er m, an d d ecr ease the n eed for cesar ean d eliver y. It is u n clear wh et h er this pr oph ylaxis is u sefu l for t h ose wit h out a recurrence during pregnancy, yet many practitioners will recommend prophylaxis. Use of acyclovir for suppression has also been found t o be safe in breastfeeding mot hers. At t his t ime, rout ine screening for ant ibodies and suppressive t herapy for seroposit ive part ners is not recommended. The obstetrician counsels the patient about the possibility of needing cesarean when she goes into labor. H ist o r y of lesio n s n o t ed o n the vagin a 1 m o n t h p r evio u sly, n ow n o t visib le C. Which of the followingstatements is most accurate in the counseling of this patient? D ecr ease the lik elih o o d of t r an sp lacen t al t r an sm issio n t o the fet u s C. The lesions h ave ragged edges, a necrot ic base, and t h ere is adenopat h y not ed on the right inguinal region. W hich of t he following is the most likely scenario of infect ion to t his infant? W h en t h er e are n o lesio n s o r p r o d r o m al sym p t o m s, the patient should be counseled that she is at low risk for viral shedding and has an unknown risk of neonatal herpes infection; typically, the patient will opt for vaginal delivery. The posterior thigh is unlikely to inoculate the baby during delivery, and is not an indication for cesarean delivery. Lesions on the ch est wall con sist ent wit h h er p es zost er would n ot n ecessit at e cesar ean d eliv- ery; however, t he baby should st ill not come in cont act wit h t hese lesions, and breast feeding should be avoided. The rationale for oral acyclovir therapy at the primary outbreak is to decrease viral shedding and the duration of infection. The acyclovir does not affect t he likelih ood of fut ure recurrence and does not change t he pat ient ’s immune response. O ral suppressive ant iviral t h erapy beginning at 36 weeks should also be considered in t his pat ient t o reduce t he chance of viral shed- ding and recurrence near the time of delivery. There is no evidence that oral acyclovir alt ers t ransplacent al t ransmission t o t he fetus, alt hough reducing t he vir em ia m ay h elp. Chancroid is a rare cause of infectious vulvar ulcers in the United States, alt hough worldwide it is quit e common; t hus, cases occurring in t he United St ates are related to port s of ent ry. G en it al h er- pes can cause recurrent painful genital sores, and herpes infection can become severe in people who are immunosuppressed. Syphilis t yp ically p r esen t s d u r in g the first stage of the disease as a small, round, and painless chancre in the area of the body exposed to the spirochete. The Bartholin glands, responsible for vagin al secr et io n s, are lo cat ed at the en t r an ce of the vagin a ; they m ay en lar ge into painless abscesses when they become clogged and infect ed. Vulvar car- cin oma t ypically is n ont en d er, u lcer at ive, an d is m or e com mon in p ost men o- pausal women. Th e s e a r e u s u a l l y d u e t o p r i m a r y o r n o n p r i m a r y f i r s t e p i s o d e i n fe c t i o n s. The patient states that 4 weeks previously, after she had engaged in sexual intercourse, she experienced some vaginal spotting. Fo u r week s p r evio u sly, sh e exp er ien ced so m e p o st co it al vagin al spotting.
Full renal compensation takes days and even then may be impaired because of coexisting renal dysfunction sildalis 120mg. However 120 mg sildalis, acidosis is the component of hypercapnia that seems to be associated with many of the potentially beneﬁcial physiological effects sildalis 120 mg, e 120mg sildalis. This is consistent with the often disappointing physiological effect of buffering acidosis (metabolic or respiratory) in critically ill patients . Our practice is outlined below , but the overall approach to hypercapnia is valid no matter the precise levels individuals choose . In an ideal world , we would only intervene if there were physiological problems associated with hypercapnia . In the real world of very unwell patients with several diagnoses and comorbidities , attributing physiological changes to hypercapnia is well nigh impossible. Unresponsive hypercapnia is most often accompanied by signiﬁcant oxygenation difﬁculty. It is useful to have a systematic approach to this emergency committed to midbrain, thereby freeing up your cortices to think about what is actually going on. This chapter will deal with sudden respiratory deterioration, although in practice the respiratory and cardiovascular systems are inextricably linked. Oxygen cascade There has been an interruption in the delivery of oxygen from the hospital supply to the patient’s cells. Hand ventilation Diagnostic information Hand ventilation will provide diagnostic information. The therapeutic advan- tage of hand ventilation is the delivery of tidal volumes and airway pres- sures that in normal circumstances would be inappropriate, and that you would never set on a ventilator. These pressures are usually delivered with no real monitoring (next time you hand ventilate a patient use a ﬂow meter/pressure gauge and measure what you are doing: you will be surprised! In the short term this will rarely do harm, but beware unilateral chest movement: it is possible to quickly convert a pneumothorax to a life — threatening tension pneumothorax with these pressures. Ventilator and circuit • Check the ventilator monitors, particularly airway pressure and expiratory tidal volume. Bronchospasm In acute severe asthma there will usually be some air entry with associated wheeze and prolonged expiration, but sometimes the bronchospasm is so severe that it is nearly impossible to move air into the chest and the chest is silent. Allow expiration to be as full as possible, even if that means disconnecting after every breath. As well as the clinical signs above, expiratory times are usually shorter and the characteristic shape of the ﬂow volume loop seen in bronchspasm is missing. Malignant arrhythmias • The cardiovascular response to arrhythmias depends on the type of arrhythmia, the ventricular rate, and pre-existing cardiac disease. Sedation requirements vary widely between patients and within individual patients at different stages of their critical illness. A systematic assessment of the needs of each patient is required to achieve optimum sedation where patient comfort is achieved without exposing them to the adverse effects of excessive sedation. For example, early during critical illness requirements may be high because patients require tracheal intubation, controlled mechanical ventilation, analgesia for underlying conditions, and anxiolysis. If advanced ventilatory strategies are required, there may be patient–ventilator asynchrony, especially if there is a high respiratory drive as a result of hypercapnia or hypoxaemia. Under these circumstances optimum sedation may be complete unconsciousness for many patients. Optimum sedation is therefore the most appropriate level of sedation for an individual at the time of assessment. The challenge during routine management is to recognize changing sedation requirements, especially the transition to greater tolerance of consciousness. It is best achieved by incorporating sedation assessments in routine management and enabling multiple members of the multidisciplinary team to alter the level of sedation within agreed guidelines. Relationship between sedation practice and outcome Signiﬁcant heterogeneity exists in trial design, trial quality, the population studied, the control group practice, and the interventions employed in trials of sedation practice and outcome. Overall, however, these trials provide strong evidence that optimizing sedation practice improves patient outcomes (Table 5. Acute illness-related ventilation or advanced hepatic) factors respiratory support Hepatic or renal failure Painful conditions, e. Shock burns, multiple trauma Hypothermia Cerebral oedema Low illness severity Fig. A clinical sedation scale that uses patient responses to simple stimuli should be used to categorize a patient’s level of sedation at regular intervals. Assessment starts with observation and progresses through non-physical and then physical stimuli. If so, the score is 0 to +4: 0, Alert and calm; +1 Restless (anxious but movements not aggressive or agitated); +2, agitated (frequent non purposeful movements, ﬁghting the ventilator); +3 Very Agitated (pulls or removes tubes or catheters, aggressive); +4 Combative (overtly combative, violent, immediate danger to staff). They may be –1, Drowsy (opens eyes and sustains eye contact for >10 seconds); –2, Lightly Sedated (non sustained eye opening and eye contact < 10seconds); –3 Moderately Sedated (moves or has eye opening, but no eye contact). They may be –4, Deeply Sedated (moves or opens eyes); –5, Unarousable (no response). Regular recording of clinical sedation scores on patient charts at pre-agreed intervals is a useful method of ensuring regular assessment. This approach can result in signiﬁcant over-sedation because it fails to distinguish continuous from intermittent requirements. In conscious patients visual analogue scales or rating scales can be used, but this is not possible in unconscious or delirious patients. Systematic use of this scale during procedures such as physiotherapy is well-suited to guiding boluses of sedation or analgesia. Rate of drug elimination The elimination of most sedative drugs is an exponential process described by the equation of ﬁrst-order metabolism: Ct = C0e–kt where Ct = concentration at time t, C0 = initial concentration, and k = rate constant. The elimination rate constant is the fraction of the total amount of drug in the body that is removed per unit time. It depends on volume of distribution and clearance (altered by protein binding, and renal and hepatic function). Active metabolites Accumulation of active metabolites is also important, especially if their elimination is unpredictable. Side effect proﬁles • Cardiovascular instability is of particular relevance in critically ill patients because of the high prevalence of shock. Cost Sedative agents account for a signiﬁcant proportion of total drug cost in intensive care. Sedative drugs The relevant properties of commonly used classes of sedative agents are described below and summarized in Table 5. They can be given by intermittent bolus (lorazepam) or by continuous infusion (midazolam). Recently, several studies have highlighted the potential adverse effects of these agents: • Unpredictable kinetics in patients with renal and hepatic dysfunction. It has the advantage of more predictable kinetics even in the presence of organ dysfunction, and a lack of active metabolites. However it is associated with more hypotension and cardiovascular instability, especially when administered in bolus dose. High propofol doses (>4mg/kg/h) for prolonged periods have been associated with rhabdomyolysis, cardiovascular collapse, hepatic dysfunction, and renal failure—the ‘propofol infusion syndrome’. Most cases have been described in children and as a result propofol is not used for continuous sedation in this group. Reported advantages include: • A dose dependent hypnotic effect • Some analgesic properties • Sympatholysis, resulting in less ‘swings’ in blood pressure and heart rate • Predictable pharmacokinetics and a short duration of action in patients without renal and hepatic impairment. Clonidine has more generalized central and peripheral activity, whereas dexmedetomidine is primary centrally acting and has been developed pri- marily for sedation. Duration of mechanical ventilation was reduced compared with midazolam despite both trial groups achieving similar high levels of optimum sedation. These data suggest that dexmedetomidine may have class- speciﬁc advantages over existing agents, although licensing approval for routine use is awaited. The most commonly used agents are morphine, fentanyl, alfentanil, and remifentanil. Metabolism is predominantly hepatic, and their clearance is not dependent on renal function. Remifentanil • Remifentanil is an ultra-short-acting agent with highly predictable kinetics even in the presence of organ failure. The overall quality of trials was low, making ﬁrm recommendations about the beneﬁt of remifentanil difﬁcult. Effective protocols empower nursing staff to adjust doses of sedative and analgesic drugs in response to clinical sedation scores to achieve the target sedation level. Simple checklists can deﬁne patients in whom nurses can reduce sedation and commence weaning trials (see box). No or minor requirement for cardiovascular support with vasopressors or inotropic drugs. Implementing protocols Implementing and maintaining practice change requires planning, edu- cation, and regular audit. Sedation holds • A sedation hold is a period during which continuous sedation is stopped, usually until the patient regains consciousness. Sedation monitors Sedation monitors are devices which attempt to measure conscious level by analysing cortical electrical activity. Although the output from these devices correlates with sedation state, they have poor discrimination for different sedation states and are not widely used. There is no evidence at present that these monitors are more effective than clinical protocols. It can occur in patients who have required large doses of sedative and analgesic drugs, especially for prolonged periods. Sedation withdrawal syndromes typically include tach- ycardia, hypertension, sweating, and agitation. Different drug classes, especially α2-agonists such as clonidine, are sometimes effective during withdrawal syndromes. T hepat ient may bebe e on a pat ient iggeed mode, w hich may enabledeceasedsedat ion dose. T his is t he most likely causeofagiat ion at his st age Pat ient hype ensive achycar dic, andagiat ed Ifdeliiumis pr esent, cont olagiat ion w ih halopeidolboluses andpr escibe w hen r egainingconsciousness egular halopeidol o ensur e hepat ient eceives a maint enancedose N ot obeyingsimplecommands C heck heusualpr eillness medicat ion. Reint oduceant ihype ensives andor N ur sehas r esedat edfor similar picur eseveal heapy for ischaemichear disease, pr efeably via t henasogast ic out e t imes A geea st aged educion st at egy in sedat ivedugdoseove henext –4 h. T hesedat ion Y oungmale auma pat ient w ihout headinjur y) T his is pr obably pr edominant ly a sedat ion w ihdaw alsyndome w ihdaw alcycle w ho r equiedhigh doses ofsedat ion and A at ionaleappr oach w ouldbe analgesia ( midazolam, pr opofol, andmor phine C heckfor hepr esenceofdeliiumand eat w ih halopeidolifpr esent dur ingheacut ephaseofillness, w hich included Ensur eadequat eanalgesia, especially in view ofhist or y. Interest in the prev- alence, pathogenesis, prevention, and treatment of delirium has increased signiﬁcantly in recent years because it is independently associated with prolonged hospitalization, higher short- and long-term mortality, and poorer long-term cognitive function after critical illness. This method has low intra- and inter-rater variability and is the method of choice in mechanically ventilated patients. Yes No Or 1B:Has the patient had any fluctuation in mental status in the past 24 hours as evidenced by fluctuation on a sedation scale (e. Feature 2: Inattention Positive Negative Positive if either score for 2A or 2B is less than 8. If pt is able to perform this test and the score is clear, record this score and move to Feature 3. Feature 3: Disorganized thinking Positive Negative Positive if the combined score is less than 4 3A: Yes/No Questions (Use either Set A or Set B, alternate on consecutive days if necessary): Combined score (3A+3B): Set A Set B (out of 5) 1. Score—(Patient earns 1 point for each correct answer out of 4) 3B: Command Say to patient: “Hold up this many fingers” (Examiner holds two fingers in front of patient) “Now do the same thing with the other hand” (Not repeating the number of fingers). A key issue is to stop or avoid factors that perpetuate or exacerbate delirium, correct reversible factors that could be contributing, and switch to using antipsychotics for agitation. Most guidelines recommend ‘typical’ antipsychotics, usually haloperidol in small (1. The effectiveness and safety of newer ‘atypical’ antipsychotics, such as olanzapine, is unknown. At present it is unclear whether patients with hypoactive delirium beneﬁt from antipsychotic treatment. No specific pharmacological Titrate haloperidol to achieve management control (2–10mg every 30min) Regular haloperidol to maintain control (typically 25% dose required for control every 6h) Fig. This is often due to: • Factors relating to the underlying illness: • Stress response • Pain • Inﬂammation • Encephalopathy. There is strong evidence that a systematic method for assessing and managing sedation using clinical tools and protocols can improve patient outcomes and quality of care. Avoiding unnecessary over-sedation is particularly important to improve patient outcomes and reduce illness costs. Risk of transfer must therefore be weighed against the beneﬁt to the patient and the decision to transfer should involve a senior experi- enced doctor. The keys to safe patient transfer are: • Thorough assessment • Preparation for both expected and unexpected situations • Good communication. Stafﬁng Specialist transfer teams are recommended, but the referring hospital often provides staff for the transfer. As the transfer team works with no immediate support the team members should be suitably experienced. Potential adverse events during transfer Although there is limited information on the rates of adverse events during patient transfer, they may be potentially catastrophic. Communication • Ensure good communication within the team: understand everyone’s roles, skills, and limitations. This may be due to a lengthy period of being supine, frequent ventilator circuit manipulation, and inadequate airway suctioning. How to avoid problems during transfer Patient assessment prior to transfer Thorough assessment and stabilization prior to transfer will minimize the need for interventions en route. Familiarity with the patient’s clinical condi- tion will help rapid identiﬁcation of changes. Have a low threshold for insertion of new chest drains prior to departure • Cardiovascular: • Clinical examination • Current intravenous access adequate? Although some unstable patients need to be transferred for deﬁnitive management (e.
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