Agents In Infants Research Articles

Analgesia for dying infants whose life support is withdrawn or withheld.

To determine the frequency of opiate analgesia administration to infants when life support is discontinued and to determine whether infant characteristics, such as birth weight and diagnosis, or the physician's reasons for discontinuing life support influence either the decision to provide opioid agents or the dosages administered. We reviewed all 165 deaths in a 3-year period at a university-based level III intensive care nursery. Of the 121 deaths attributable to withdrawal or withholding of mechanical ventilation and/or extracorporeal membrane oxygenation, we ascertained whether opioid analgesics (morphine sulfate [MS] or fentanyl) were administered either concurrent with or after life-support withdrawal and at what doses. We examined whether these end-of-life practices varied according to birth weight, diagnoses, and the reasons documented by the neonatologist for discontinuing life support. Opioid analgesia was provided to 84% of infants as their life support was either withheld or withdrawn. Infants with necrotizing enterocolitis and major anomalies or chromosomal disorders were more likely to be given opiates than infants with other diagnoses. Birth weight was not different for infants who received opiates compared with those who were not given opiates. Opioid analgesia was provided to all 18 infants for whom physicians documented the patients' suffering as a reason to discontinue life support. Sixty-four percent of infants who received opiates were given doses in the usual pharmacologic range of 0.1 to 0.2 mg/kg MS. Of the 36 infants given more than 0.2 mg/kg MS, all but 2 were receiving ongoing treatment with opioid agents. In most cases of withholding or withdrawal of life support in critically ill infants, neonatologists provided opioid analgesia to these infants at the end of life, despite the potential respiratory depression of opioid agents in infants whose respiratory support is discontinued.

Direct Myocardial Effects of Halothane and Isoflurane

Infants may be more sensitive than adults to myocardial depression by potent inhalation anesthetics. Most studies of cardiovascular effects of inhalation agents in infants are performed in vivo with multiple factors producing the observed effects. The purpose of this study was to determine if newborns are more sensitive than adults to the direct actions of halothane and isoflurane on global electrophysiologic, contractile and metabolic functions of the heart. Direct myocardial effects of the agents were determined using isolated rabbit hearts perfused at constant pressure. Three doses of halothane and isoflurane were administered to 37 infant (3-8 days old) and 36 adult rabbit hearts. Heart rate and rhythm, atrioventricular conduction time, left ventricular function (systolic, diastolic, and developed pressures; maximum and minimum values of the differential wave (dP/dt); and time constant of isovolumic LV relaxation), coronary flow and O2 consumption, and fractional O2 extraction were measured and compared between age and anesthetic groups. Halothane was a more potent depressant of cardiac function than isoflurane and developmental differences were more evident with this agent. The most striking developmental differences in anesthetic effects were the significantly greater prolongation of atrioventricular conduction time and the time constant of isovolumic LV relaxation by halothane in infant compared with adult hearts. Infant hearts were also more sensitive to depression of left ventricular developed pressure and maximum value of the differential wave and to elevation of diastolic pressure by halothane. For both agents heart rate was less depressed in infants than in adults. There were no developmental differences in anesthetic effects on coronary flow and O2 metabolism. Developmental changes in myocardial physiology make the newborn less sensitive to direct depression of heart rate by halothane and isoflurane, but more sensitive to depression of contraction-relaxation and atrioventricular conduction by halothane.

Antiretroviral therapy for infection due to human immunodeficiency virus in children.

Infection with human immunodeficiency virus type 1 (HIV-1) in children presents problems that greatly differ from those seen in adults. The great majority of children are infected either during gestation or at the time of birth. As Drs. Pizzo and Wilfert note in their AIDS Commentary, this results in rapid development of immunosuppression and clinical manifestations in patients whose immune systems are in the process of maturing. Thus, a thorough understanding of the pharmacokinetics of antiretroviral agents in infants and small children is required. This AIDS Commentary provides a comprehensive review of the current state of our knowledge and possible future directions for the management of HIV-1 infection in this young population

Duration of action of an equipotent dose of vecuronium in infants and in children

SummaryDuring general anaesthesia without any volatile anaesthetic agents, ten infants and ten children received incremental doses of vecuronium to achieve a 95% neuromuscular block. Thereafter, the thenar electromyographic response was allowed to recover spontaneously. Total dose of vecuronium to establish a 95.0 ± 0.5% (mean ± SEM) neuromuscular block was 66% greater for children than for infants (73 ± 4 vs. 44 ± 4 μg·kg−1, P < 0.0001). However, recovery index and time to complete recovery of the neuromuscular function were 88 and 89% longer, respectively, in infants than in children (P < 0.0001). These results of the effect of an equipotent dose of vecuronium in infants and in children confirm that vecuronium is a long acting neuromuscular blocking agent in infants.

Entero-adherent Escherichia coli is an important diarrhoeagenic agent in infants aged below 6 months in Calcutta, India.

Escherichia coli adherent to HEp-2 and HeLa cells were isolated from the faeces of 43 (19.7%) of 218 hospitalised infants aged below 6 months with acute diarrhoea. No conventional virulence factors, including enterotoxin production--heat-labile (LT) or heat-stable (ST), the verotoxin (VT) or shiga-like toxin (SLT)--or the invasive phenotype (determined by the Sereny test) could be detected among these isolates. Out of the 43 isolates, 16 (37.2%) were of the known enteropathogenic O:K serogroups--enteropathogenic E. coli (EPEC). The remaining 27 (62.8%) isolates showed different types of adherence to HEp-2 and HeLa cells which was diffuse (40.7%), localised (37.0%), or both (22.3%); they were identified as entero-adherent E. coli (EAEC). The EAEC isolates adhered to HEp-2 and HeLa cells in the presence of mannose, lactose, fucose, galactose, and fetuin, indicating that adhesion was not specific for these sugars or glycoprotein. Haemagglutination and the salt aggregation test (SAT) did not correlate with patterns of adherence. The results of this study indicate that LA-EAEC is an important aetiological agent of acute diarrhoea in infants aged below 6 months in Calcutta.

Myoneural blocking agents in infants: a review

Myoneural blocking agents in infants: a review

Considerations for the Evaluation of Antiretroviral Agents in Infants and Children Infected with Human Immunodeficiency Virus: A Perspective from the National Cancer Institute

Human immunodeficiency virus (HIV) infection in infants and young children differs in a number of ways from that in adults. In most HIV-infected children the infection is acquired perinatally and the course of infection is more accelerated than in adults. Diseases related to B cell defects and dysgammaglobulinemia (e.g., multiple or recurrent bacterial infections) predominate early in the disease, and children can be symptomatic before their CD4+ count decreases. Lymphoid interstitial pneumonitis occurs frequently and almost exclusively in children, and a number of the opportunistic infections (e.g., cryptococcosis, toxoplasmosis) or malignancies (e.g., Kaposi's sarcoma) occur infrequently in children. A major disease manifestation in the pediatric population is HIV encephalopathy, which results in impairment in neurologic development that can lead to loss or lack of developmental milestones and to diminished intellectual function. The methodology and design of clinical trials for the study of pediatric HIV infection should consider these clinical and laboratory manifestations as well as the developmental differences that reflect the disease in infants and young children.

New drugs and new understandings of paediatric pharmacology

lnhalational anaesthetic agents The uptake and elimination of the inhaled anaesthetic agents in infants and children have been extensively studied. The high level of alveolar ventilation compared to the functional residual capacity, the larger proportion of vessel rich tissues, and a lower blood gas solubility coefficient all contribute to the rapid induction and recovery phases which occur in the infant. Inhalation anaesthetic agents are probably metabolized less in infants than in older patients; serum bromide levels are lower following halothane in infants than in adults. Serum inorganic fluoride levels are lower following enflurane anaesthesia, but this may also be due to increased bone deposition of fluoride in paediatric patients. The effects of the volatile anaesthetics on the cardiorespiratory system of infants and chidren are now more fully documented, lsoflurane causes an increase in heart rate and halothane slows the heart. At equal levels of anaesthesia, halothane and isoflurane cause a similar degree of hypotension which is dose-related. Isoflurane, however, causes less depression of myocardial contractility but more afterload reduction than halothane. Cardiac output is better maintained with isoflurane provided fluid is administered to maintain preload. 2 The addition of nitrous oxide to the inspired gas mixture results in cardiovascular effects which are similar to those produced by equianaesthetic dose levels of the volatile agents in oxygen. 3 While the volatile anaesthetics all cause similar increases in end-tidal carbon dioxide levels in spontaneously breathing children the patterns of ventilation differ. Depression of the ventilatory response to carbon dioxide is dose-dependent. Halothane causes tachypnoea, isoflurane causes little change in rate, and enflurane tends to slow ventilation. 4 Intercostal muscle activity is suppressed by haiothane, paradoxical breathing occurs at end-tidal concentrations above one per cent. 5 Intravenous anaesthetics and analgesics The dose requirements of thiopentone in infants and children of various ages show wide variation. Newborn infants require 3-4 mg.kg -I while those of 1-6 mo require 7-8 mg.kg-~. 6 In healthy children 5-6 mg. kg-i is the dose required for rapid reliable induction of anaesthesia. 7 The pharmacokinetics of thiopentone in paediatric patients have been studied and show a shorter elimination time in infants and children than in adults) The narcotic analgesics have been widely used in infants, especially for major surgical procedures, fentanyl being the most commonly used drug. The dose response of neonates to fentanyl indicate that a dose 10-12.5 I~g kg -I will prevent any response to surgical stimulation and provide anaesthesia for 60-90 min. 9 Older infants may require higher doses. I~ The pharmacokinetics of fentanyl depend upon age. Neonates show wider variation and slower clearance rates than older infants, who may demonstrate clearance rates higher than those of adults. ~ Preterm infants and neonates with increased intraabdominal pressure predictably demonstrate a prolonged elimination half-life of the drug. J2 Some infants demonstrate secondary peaks in plasma levels of the drug and these may be associated with respiratory depression in patients not on mechanical ventilation. The cardiovascular system is little affected by even large doses of fentanyl, but a useful effect in blunting the neonatal pulmonary vascular responses to stress has been noted. Chest wall compliance is significantly reduced by fentanyl in children.

Antimicrobial Agents in Pediatrics

For proper use of antimicrobial agents in infants and children, special precautions should be taken. These include knowledge of the pharmacokinetic properties of these agents, especially in neonates, and of host factors related to gestational and chronological ages of the patient. Failure to recognize such factors can result in either lack of therapeutic response of drug-related adverse effects. In this article, special aspects of the pharmacokinetics of antibiotics and the clinical pharmacology and indications for use of the beta-lactam antibiotics in infants and children are presented.

Comparison of the hemodynamic and echocardiographic effects of sufentanil, fentanyl, isoflurane, and halothane for pediatric cardiovascular surgery

Sufentanil, fentanyl, halothane, and isoflurane were compared as sole anesthetic agents in 48 infants and children aged 6 months to 9 years, undergoing repair of congenital heart defects. Patients were randomly assigned to receive sufentanil, 20 μg/kg, fentanyl, 100 μg/kg, isoflurane, 1.6%, or halothane, 0.9%, along with pancuronium, 0.08 mg/kg, for induction and maintenance of anesthesia. Cardiovascular function was measured by echocardiography prior to induction, postinduction, and postintubation. Systemic arterial pressure and heart rate were also recorded. Left ventricular ejection fraction (LVEF) decreased following induction with each agent: sufentanil 9%, fentanyl 9%, isoflurane 4%, and halothane 8%. Following intubation LVEF increased in the sufentanil, fentanyl, and isoflurane groups, but LVEF remained 13% below baseline values in the halothane group. Five of the 12 patients in the halothane group had a LVEF less than 55%. Arterial pressure immediately prior to bypass was significantly less than baseline in each group; however, arterial pressure was higher in the narcotic groups during isolation and cannulation of the great vessels. It is concluded that halothans, 0.9%, used as an induction agent in infants and children undergoing cardiac surgery causes a clinically significant decrease in LVEF. Based on the echocardiographic data, sufentanil, fentanyl, and isoflurane as used in the present study do not have a clinically significant effect on cardiac function and may offer an advantage to infants and children with marginal cardiovascular reserve.

A Practical Guide to the Diagnosis of Congenital Infections in the Newborn Infant

Every attempt should be made to identify an etiologic agent in infants with suspected congenital infection. Some of the infections are treatable, such as herpes simplex, syphilis, and toxoplasmosis. For other infectious agents (i.e., CMV and rubella), close follow-up will enable early detection of hearing impairment and permit early educational intervention. In addition, appropriate isolation measures will reduce the risk of nosocomial infections due to herpes simplex, rubella, hepatitis B, and CMV. Rational use of the available diagnostic tools will enable detection of most symptomatic congenitally infected neonates at a reasonable cost.

Necrotizing enterocolitis: factors affecting mortality in 101 surgical cases.

One hundred one infants requiring operative treatment for necrotizing enterocolitis were evaluated for prenatal, perinatal, therapeutic, clinical, laboratory, radiographic, and operative factors as they relate to mortality. Infants less than 28 weeks gestation and those with birth weight less than 1500 gm had an increased mortality rate. The use of umbilical arterial catheters, high-density premature formulas, and aminophylline (for apnea) had an adverse effect on survival. Persistent acidosis, oliguria, and abdominal wall erythema resulted in a significantly worse outcome. The presence of portal vein air on abdominal radiograph was associated with a 71% mortality rate. The survival rate in infants with localized involvement was 70%. Thirty-eight percent of patients had extensive bowel involvement and a greater than 95% mortality rate. Avoidance of enteral feedings, cautious use of umbilical artery catheters, and judicious application of pharmacologic agents in infants at risk for necrotizing enterocolitis is of importance with regard to prevention. While medical management is feasible in some cases, persistent acidosis, oliguria, abdominal wall erythema, and portal vein air are associated with advanced disease. Infants with these risk factors should be candidates for prompt operative intervention.

Determinants of the diuretic response to furosemide in infants with congestive heart failure.

A wide interindividual variation in the degree of diuresis produced following treatment with furosemide has been observed in infants with congestive heart failure. A method of pharmacokinetic analysis that separates drug disposition from renal response to furosemide was used to compare the effect of this agent in infants with congestive heart failure with the effect seen in infants with fluid retention secondary to noncardiac factors. No differences in the drug elimination rate, urinary drug excretion, or renal diuretic response between the 2 groups were seen. Infants in both groups exhibited a wide range in all variables examined. The marked interindividual variation in response originates from decreased delivery of furosemide to its site of action in some patients and a decreased responsiveness to the drug in others.

Lack of stimulation of isohemagglutinin antibodies byimmunization with group B streptococcal (Type III) vaccine

Rodriguez W J, Kim HW, Arrobio JO, Brandt CD, Chanock RM, Kapikian AZ, Wyatt RG, and Parrott RH: Clinical features of acute gastroenteritis associated with human reovirus-like agent in infants and young children, J PEDIATR 91:188, 1977. Davidson GP, Bishop RF, Townley RRW, Holmes IH, and Ruck BJ: Importance of a new virus in acute sporadic enteritis in children, Lancet 1:242, 1975. 3. Davidson GP, and Barnes GL: Structural and functional abnormalities of the small intestine in infants and young children with rotavirus enteritis, Acta Paediatr Scand 68:181, 1979. 4. Hyams JS, Stafford RJ, Grand RJ, and Watkins JB: Correlation of lactose breath hydrogen test, intestinal morphology, and lactase activity in young children, J PEDIATO, 97:609, 1980. 5. Hamson M, and Walker-Smith JA: Reinvestigation of lactose intolerant children: lack of correlation between continuing lactose intolerance and small intestinal morphol. ogy, disaccharidase activity and lactose tolerance tests, Gut 18:48, 1977. 6. Yolken RH, Kim HW, Clem T, Wyatt RG, Kalica AR, Chanock RM, and Kapikian AZ: Enzyme-linked immunosorbent assay (ELISA) for detection of human reovirus-like agent of infantile gastroenteritis, Lancet 2:263, 1977. 7. Perman JA, Barr RG, and Watkins JB: Sucrose malabsorption in children. Noninvasive diagnosis by interval breath hydrogen determination, J PEI~IATI~ 93:17, 1978. 8. Gardiner A J, Tarlow M J, Sutherland IT, and Sammons HG: Lactose malabsorption during gastroenteritis, assessed by the hydrogen breath test, Arch Dis Child 56:364, 1981.

A new approach to the use of antifungal agents in infants with persistent oral candidiasis

11. Loughnan PM, Greenwald A, Purton WW, Aranda JV, Watters G, and Neims AH: Pharmacokinetic observations of phenytoin disposition in the newborn and young infant, Arch Dis Child 52:302, 1977. 12. Painter MJ, Pippinger C, MacDonald H, and Pitlick W: Phenobarbital and diphenylhidantoin levels in neonates with seizures, J PEDIATR 92:315, 1978. 13. Yaffe SJ, and Stern L: Clinical implications of perinatal pharmacology, in Mitkin BC, editor: Perinatal pharmacology and therapeutics, New York, 1976, Academic Press, Inc., pp 389-396. 14. Hendeles L, Weinberger M, and Wyatt R: Guide to oral theophylline therapy for the treatment of chronic asthma, Am J Dis Child 132:876, 1978.

Staphylococcal pyomyositis in South Texas

7. Tallett S, MacKenzie C, Middleton P, Kerzner B, and Hamilton R: Clinical, luborutory and epidemiologic features of II viral gnstroenterltis in infants and children, Pediatrics 60:217, 1977. 8. Davidson OP, Bishop RF', Townley RRW, Holmes IH, and Ruck OJ: Importance of a new virus in acute sporadic enteritis in children, Lancet 1:242, 1975. 9. Rodriguez WJ, Kim HW, Arrobio JO, Brandt ED, Chanock RM, Zapikian AZ, Wyatt RO, and Parrott RH: Clinical features of acute gastroenteritis associated with human reovirus-like agent in infants and young children, JPEDIATR 91:188, 1977. 10. Berthiaume L, Alain R, McLaughlin B, and Chagnon A: Use of human gamma-globulin as a first step screening reagent for routine viral infection diagnosis, Proc Microscopic Soc Canada 4:64, 1977.

ACUTE GASTROENTERITIS AMONG SCHOOLCHILDREN ASSOCIATED WITH REOVIRUS-LIKE AGENT

During early summer 1975 and spring 1976, outbreaks of acute gastroenteritis were reported from primary schools and other institutions in several districts of Japan. Outbreaks occurred in an explosive manner resembling mass food poisoning from a school lunch. The majority of patients were in the age group 6-14 years. Clinical features were generally mild, consisting of vomiting and/or diarrhea, often with low-grade fever. Reovirus-like agents in the feces were found in 27 (44%) of 62 patients. The virus found in feces of schoolchildren with acute gastroenteritis (SCGV) was related morphologically as well as serologically, not only to the agent found in infantile gastroenteritis (IGV), but also to neonatal calf diarrhea virus (NCDV). A slight difference in antigenicity between SCGV and IGV as suggested by cross complement fixation (CF) remains to be elucidated. About one-half of paired sera from 54 patients showed a significant rise in CF antibody against SCGV and/or NCDV. The pattern of neutralizing (NT) antibody against NCDV in patients' sera was similar to that of CF antibody. Most children studied had a titer of 1:4 or greater of CF and/or NT antibodies to SCGV and NCDV in acute sera. The relationship between acute gastroenteritis associated with reovirus-like agent in infants and that in schoolchildren is discussed.

Clinical features of acute gastroenteritis associated with human reovirus-like agent in infants and young children

Between January, 1974, and June, 1975, infection with a human reovirus-like agent was detected in 47% of 152 infants and children hospitalized with acute gastroenteritis. Certain epidemiologic, clinical, and laboratory findings appear to be helpful in distinguishing gastroenteritis due to HRVLA from other causes in those children sick enough to require hospitalization. Age: 76% of infants and children seven through 12 months of age and 76% of those 13 through 24 months of age had infection with the HRVLA, whereas such infection was found in only 21% of infants under six months of age and 23% of children 25 through 60 months of age. Time of Year: 61% of patients studied during the cooler months had HRVLA infection and such infection was not found from June to October. Frequency of vomiting and dehydration: Twice as many patients infected with HRVLA as those who were not had vomiting (92%) and significant dehydration (83%).

Airway closure in children.

Airway closure in children.

Transplacental passage of antibody to western equine and St. Louis encephalitis viruses.

SummaryExaminations for the presence of neutralizing antibody to the Western equine encephalitis (WEE) and St. Louis encephalitis (SLE) viruses were made of blood specimens from parturient mothers residing in an endemic area of Western equine and St. Louis encephalitis. It was found that 11 per cent of the mothers studied possessed neutralizing antibody to the WEE virus and 27 per cent possessed neutralizing antibody to the SLE virus; there also was evidence of a direct relationship between the length of residence in the area and the acquisition of such antibody.It was found that both complement-fixing and neutralizing antibodies to these two viruses readily pass the placenta, but no evidence was obtained that the difference between the proportion of infants possessing antibody to the WEE virus and those possessing antibody to the SLE virus is responsible for the remarkable difference in the attack rates of these two agents for infants. The temporal persistence of passively acquired neutralizing antibody to the WEE and SLE viruses appeared to be no greater than that reported for antibodies to other viral agents.