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Prevention of iatrogenic neonatal respiratory distress syndrome: elective repeat cesarean section and spontaneous labor.

Neonatal respiratory distress syndrome (RDS) is an important complication of elective repeat cesarean section. In a review of 68,880 consecutive deliveries, 1,897 women underwent elective cesarean section at a gestation estimated to be greater than or equal to 38 weeks. Seventy-one (4.3%) of the infants of the 1,649 women who were not in labor at the time of delivery developed neonatal RDS. None of the infants of the 248 women who were in spontaneous labor at the time of delivery developed RDS (P less than 0.005). There were no cases of uterine rupture in either group. Of the 71 infants who developed RDS, 29 (41%) were judged to be at term on the basis of both examination and birth weight. Misapplication of fetal ultrasound data contributed to the premature delivery of more than one third of the infants with RDS. Awaiting the onset of spontaneous labor to determine the timing of repeat cesarean section in women at term is an effective way to preventing iatrogenic neonatal RDS.

Cesarean Section↗

Thirty years of clinical trials in acute respiratory distress syndrome.

OBJECTIVE: To systematically review clinical trials in acute respiratory distress syndrome (ARDS). DATA SOURCES: Computerized bibliographic search of published research and citation review of relevant articles. STUDY SELECTION: All clinical trials of therapies for ARDS were reviewed. Therapies that have been compared in prospective, randomized trials were the focus of this analysis. DATA EXTRACTION: Data on population, interventions, and outcomes were obtained by review. Studies were graded for quality of scientific evidence. MAIN RESULTS: Lung protective ventilator strategy is supported by improved outcome in a single large, prospective trial and a second smaller trial. Other therapies for ARDS, including noninvasive positive pressure ventilation, inverse ratio ventilation, fluid restriction, inhaled nitric oxide, almitrine, prostacyclin, liquid ventilation, surfactant, and immune-modulating therapies, cannot be recommended at this time. Results of small trials using corticosteroids in late ARDS support the need for confirmatory large clinical trials. CONCLUSIONS: Lung protective ventilator strategy is the first therapy found to improve outcome in ARDS. Trials of prone ventilation and fluid restriction in ARDS and corticosteroids in late ARDS support the need for large, prospective, randomized trials.

Clinical Trials as Topic↗

The accuracy of lamellar body count and lecithin/sphingomyelin ratio in the prediction of neonatal respiratory distress syndrome: a meta-analysis.

OBJECTIVE: To compare the performance of the lecithin/sphingomyelin ratio and the lamellar body count in the prediction of neonatal respiratory distress syndrome. DESIGN: Meta-analysis. SAMPLE: Six studies reporting on the performance of both the lecithin/sphingomyelin ratio and the lamellar body count published between January 1966 and August 1999. METHODS: We performed a computerised MEDLINE search to identify articles published on the subject. For the six selected studies, prevalence of respiratory distress syndrome and sensitivity and specificity of the tests in the prediction of respiratory distress syndrome were calculated, and overall performance was assessed by constructing summary receiver-operating characteristic curves. RESULTS: The constructed summary receiver-operating characteristic curves showed the lamellar body count to perform slightly better than the lecithin/sphingomyelin ratio in the prediction of respiratory distress syndrome (P= 0.13). CONCLUSIONS: Since the lamellar body count can be performed quickly and since it is less expensive than the lecithin/sphingomyelin ratio, we recommend the former as the test of first choice in the assessment of fetal lung maturity.

Amniotic Fluid↗

An increase in serum C18 unsaturated free fatty acids as a predictor of the development of acute respiratory distress syndrome.

OBJECTIVE: No means exist for predicting the acute respiratory distress syndrome (ARDS), which complicates sepsis, trauma, and a variety of clinical disorders. Because activation of phospholipid-signaling pathways involving the acyl chains oleate and linoleate may initiate and amplify the inflammatory response, and thereby lead to the development of ARDS, we examined whether serum concentrations of these bioactive lipids increase and are predictive of ARDS in at-risk patients. DESIGN: Part I: A prospective, single-blind trial. Part II: A prospective, randomized, double-blind trial. SETTING: General intensive therapy units in five university teaching hospitals. SUBJECTS: Part I: Thirty-nine healthy control patients were studied to determine normal distribution of serum acyl values, followed by 30 patients admitted with onset of sepsis, trauma, or development of ARDS (within 24 hrs of admission) over a 1-yr period. Part II: Eight patients admitted with sepsis syndrome over a 2-month period. INTERVENTIONS: Part II: Patients were randomized to receive the substituted methylxanthine, lisofylline (CT1501R), or an identically presented placebo. MEASUREMENTS AND MAIN RESULTS: We measured the serum free fatty acid concentrations in the 39 healthy control subjects, and then we prospectively examined the serum free fatty acid concentrations in 30 age-matched patients in samples obtained within 24 hrs from the onset of sepsis, trauma, or development of ARDS. We then prospectively studied eight septic, at-risk patients who were matched for age, Acute Physiology and Chronic Health Evaluation II scores, Multiple Organ Failure index, and Glasgow Coma Score, in a double-blind, placebo-controlled, pilot study. These patients included four patients who received no treatment and four patients who received lisofylline, a compound that decreases serum unsaturated free fatty acids and diminishes acute lung injury in animals caused by sepsis and/or trauma. The calculated ratios of serum free fatty acids (Le., the ratio of C18 unsaturated fatty acids linoleate and oleate to fully saturated palmitate, C16:0) increased and predicted the development of ARDS in at-risk patients. Serum samples from the 30 patients, obtained within 24 hrs from the onset of sepsis, trauma, or development of ARDS, had significantly increased mean acyl chain ratios (1.42 +/- 0.35 [SD]) compared with healthy control subjects (0.86 +/- 0.25; p < .01). Sera from 13 patients with sepsis or trauma who did not develop ARDS (group A [at-risk, non-pre-ARDS]) also had increased acyl ratios (1.23 +/- 0.27) compared with sera from healthy control subjects (0.86 +/- 0.25; p < .01). Sera from seven patients who subsequently developed ARDS (group B [at-risk, pre-ARDS]) had higher acyl ratios (1.70 +/- 0.21) than group A at-risk patients who did not develop ARDS (1.23 +/- 0.27; p < .01) or healthy control subjects (0.86 +/- 0.25; p < .001). Sera from ten group C patients with ARDS at the time of admission to the study had the highest acyl ratios (1.80 +/- 0.75), which exceeded values for healthy control subjects (p < .001) and group A at-risk patients without ARDS (p = .01), but were not significantly different then group B at-risk, pre-ARDS patients (p = .17). Prospective study of eight septic, at-risk patients demonstrated significantly (p < .05) increased serum acyl ratios in the four untreated patients (findings consistent with the first study) but a significantly (p = .02) reduced ratio in the four at-risk patients treated with lisofyline. CONCLUSIONS: Increases in unsaturated serum acyl chain ratios differentiate between healthy and seriously iII patients, and identify those patients likely to develop ARDS. Thus, the serum acyl ratio may not only prospectively identify and facilitate the assessment of new treatments in patients at highest risk for developing ARDS, but may also lead to new insights about the pathogenesis of ARDS.

Adult↗

[Acute respiratory distress syndrome. Pathogenesis and therapy of acute pulmonary failure].

Adult respiratory distress syndrome (ARDS) is the pulmonary response to systemic inflammation precipitated by local or systemic tissue hypoxia, or ischaemia and reperfusion. ARDS is a dynamic, pathological process with a multifactorial etiology. The main clinical manifestations of ARDS are dyspnoea, non-cardiogenic pulmonary oedema, and hypoxia due to increased pulmonary capillary permeability, pulmonary vasoconstriction and diminished pulmonary vascular reactivity. Eventually this pulmonary pathology results in first, oedema, pulmonary hypertension, and increased ventilation-perfusion inequality and later, pulmonary remodelling and irreversible pulmonary hypertension. The inflammatory mechanisms involved in acute lung injury are complex and include activation of polymorphonuclear neutrophils, endothelial cells, and synthesis of free radicals, predominantly derived from oxygen. Cytokines synthesized by macrophages maintain and regulate the inflammatory host response. Immune-modulating therapy in ARDS is yet experimental. Accordingly, treatment in ARDS is supportive, directed towards pulmonary oedema, pulmonary hypertension and hypoxaemia. The use of low tidal volumes and low inspiratory pressures in mechanical ventilation is established therapy. The goal in haemodynamic monitoring by applying a Swan-Ganz catheter is to obtain a low pulmonary capillary wedge pressure (< 12-15 mmHg) without compromising adequate delivery of oxygen to vital organs. For treatment of pulmonary hypertension nitric oxide is useful. Change of position and inhalation with beta2-agonists are therapeutic possibilities. Steroids may be of benefit in the late proliferative phase of ARDS.

Humans↗

Clinical spectrum of acute respiratory distress syndrome in a tertiary pediatric intensive care unit.

Acute respiratory distress syndrome (ARDS) has been a great challenge in the field of pediatric critical care medicine. The clinical picture of children with ARDS in Taiwan has seldom been reported. The purpose of this study was to investigate the incidence, predisposing factors, clinical manifestations, strategies of ventilator support, adjuvant therapies, and prognosis of children with ARDS in a tertiary pediatric intensive care unit (PICU). A retrospective review of admissions to our PICU in the past 3 years showed that 16 cases met the criteria of pediatric ARDS. The incidence was 0.2% of all PICU admissions. The predisposing factors were varied, and pneumonia was the most common. The mean values of acute lung injury scores, ventilation indices and PaO2/FiO2 on admission were 3.6 +/- 0.5, 68.0 +/- 32.8 and 71.6 +/- 25.2, respectively. The averages of maximal peak inspiratory pressure (PIP) and positive end-expiratory pressure (PEEP) were 40.3 +/- 9.8 and 14.0 +/- 4.6 cmH2O, respectively. Only three patients (19%) expired due to overwhelming systemic infection. Compared with our previous high mortality rate report, we emphasized gentle mechanical ventilation care, early employment of high PEEP and adjuvant therapy with sodium nitroprusside (SNP) nebulization and/or inhaled nitric oxide (iNO) to achieve an improved survival rate.

Administration, Inhalation↗

Clinical trials in adult respiratory distress syndrome.

The need for randomized clinical trials in adult respiratory distress syndrome (ARDS) is now recognized. With this recognition comes the need for researchers to implement proper trial design and for the clinician to be able to interpret results as they apply to clinical practice. The heterogeneity of ARDS as related to etiology, stage, and severity creates the potential for maldistribution of patients in the clinical trial. Likewise, a particular intervention may benefit or not benefit a patient based on these variables. Choosing a minimum of end-points (ideally one) for hypothesis testing is important. The optimal end-point for hypothesis testing pertinent to clinical impact is all-cause mortality at a certain time point (usually 14 or 28 days). Unblinded trials are suboptimal, but necessary, with interventions such as mechanical ventilation treatment modalities. Given these circumstances, treatment protocols should be utilized in both groups. Cooperation of the basic scientist and the clinical scientist is ideal for direction of research in ARDS. Industry funding of ARDS clinical trials is now typical and needed. Under these circumstances, it is important to prevent inappropriate industry influence on trial design, data analysis, data interpretation, and data presentation. The investigator must remain above reproach and the informed consent process must be of the highest standard.

Animals↗

Neuropeptides in pulmonary edema fluid of adult respiratory distress syndrome.

A role for peptidergic nerves in the adult respiratory distress syndrome (ARDS) was examined by radioimmunochemically quantifying neuropeptides in pulmonary edema (PE) fluids from seven patients with ARDS and six patients with PE from congestive heart failure (CHF). The PE fluid mean concentrations of substance P (SP) and gastrin-releasing peptide (GRP) were significantly higher in ARDS (0.59 +/- 0.29 SD and 0.10 +/- 0.03 nM, respectively, P < 0.001 for both) than in CHF (0.19 +/- 0.08 and 0.04 +/- 0.01), whereas no difference was detected between the mean levels of vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) in the two forms of PE. Mean alveolar fluid concentration of SP was 8.7 nM (range 2.1-20.5 nM, N = 4) in sheep with acute lung injury from intravenous Pseudomonas aeruginosa, but was undetectable in sheep with balloon-induced high left atrial pressure simulating CHF (N = 2) or control sheep (N = 2). Pulmonary lymphatic clearance of SP, which reflected the rate of generation of SP in the lungs, attained a maximum of 25-95 pmol/h in sheep given P. aeruginosa intravenously, but was detected in only one of four control sheep at a lower level. Some pulmonary neuropeptides thus are released locally by acute lung injury and may contribute to endothelial and/or epithelial abnormalities underlying the altered capillary-alveolar permeability in ARDS.

Adult↗

Discordance between male and female deaths due to the respiratory distress syndrome.

General neonatal mortality statistics and those for the respiratory distress syndrome (RDS) were examined for the State of Wisconsin from 1979 through 1982. The objectives were to ascertain whether there are differences in total neonatal mortality related to sex and birth weight, to determine the veracity of reported gender differences in deaths due to RDS, and to assess the contribution of other risk factors for neonatal mortality to overall and sex-specific deaths occurring secondary to RDS. Additionally, a prospective analysis was performed at one perinatal center during a 5-year period in attempts to determine whether gender remained a significant factor in deaths due to RDS after adjusting for incidence. Overall, the most frequent diagnoses in those who died were RDS (15.6%), deaths due to complications of pregnancy (8%), immaturity (4.2%), and asphyxia (3.4%). The majority of fatalities for both sexes occur in neonates weighing less than 1 kg and the percentage of deaths attributable to RDS is greatest between 1 and 1.5 kg. The difference between sexes is also maximal in the latter weight group. Deaths secondary to RDS are greater for males regardless of Apgar score at one and five minutes, mode of delivery, maternal age, or ancillary diagnosis. These data suggest that deaths secondary to RDS are consistently greater in male neonates and that delivery within a limited "window" of time during gestation increases male susceptibility to fatal RDS.

Apgar Score↗

Oxidative stress and abnormal cholesterol metabolism in patients with adult respiratory distress syndrome.

Oxidative stress has been implicated in the adult respiratory distress syndrome (ARDS). In this study, we determined the levels of selected antioxidants in the plasma of 25 patients with ongoing ARDS and 16 healthy control subjects. We also examined these plasmas and pulmonary edema fluid of ARDS patients for lipid hydroperoxides. Both ascorbate and ubiquinol-10 concentrations in ARDS plasma were significantly lower than in normal plasma. alpha-Tocopherol concentrations, when standardized to total plasma cholesterol, were not lower in ARDS patients than in normal subjects. A pattern of antioxidant levels virtually identical to that observed in ARDS plasma was obtained after in vitro incubation of healthy plasma with stimulated polymorphonuclear leukocytes: very low ascorbate, decreased ubiquinol-10, and unchanged alpha-tocopherol concentrations. Nanomolar concentrations of lipid hydroperoxides were found in pulmonary edema fluid of ARDS patients, but not in plasma, nor in the plasma of healthy individuals, when a sensitive and selective chemiluminescence assay for hydroperoxides was used. ARDS patients also showed significant decreases in plasma levels of cholesterol esters in conjunction with discoidal high-density lipoprotein profiles, indicating a decrease in lecithin-cholesterol acyltransferase activity. We conclude that ARDS is associated with oxidative stress, possibly exerted by oxidants released from activated phagocytic leukocytes, and major changes in plasma cholesterol metabolism.

Adult↗

An aggressive systematic strategy for acute respiratory distress syndrome caused by severe pneumonia after renal transplantation.

Acute respiratory distress syndrome (ARDS) caused by pneumonia after renal transplantation was usually associated with overimmunosuppression and high mortality rate. We evaluated the efficacy of an aggressive systemic protocol including strategies improving body's immune function. Twenty-one recipients were enrolled in this study. Patients were subjected to a protocol including (i) withdrawal of most immunosuppressants, (ii) early use of immunoenhancers and continuous renal replacement therapy (CRRT), (iii) reasonable administration of antibiotic regimen, (iv) prompt mechanical ventilating strategy, and (v) adequate nutrition. Immunosuppressants were adjusted according to the value of CD4+, CD8+T lymphocytes in peripheral blood. CRRT was conducted at once when patients were admitted to the intensive care unit (ICU), regardless the graft function. Thirteen (62%) survived and eight died finally. This is a high survival rate for this kind of patients. Eighteen patients had received thymosin treatment. All patients who survived experienced renal allograft dysfunction during CRRT, but when CRRT stopped, the function of all grafts gradually recovered. No acute rejection episodes were documented during the treatment. The aggressive systemic protocol including strategies improving the body's immune function and CRRT can improve the outcome of patients with ARDS after renal transplantation. The count of CD4+, CD8+T lymphocytes of peripheral blood is useful in the adjustment of immunosuppressants and the prediction of patient outcome.

Adjuvants, Immunologic↗

Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality.

The adult respiratory distress syndrome (ARDS) is characterized by increased neutrophils within the airspaces of the lungs. In order to determine if neutrophil activating protein (NAP)-1/interleukin-8 (NAP-1/IL-8) could be an important cause of neutrophil influx and activation in ARDS, we examined fluid, which was either directly aspirated or lavaged with saline from the lungs of patients with ARDS. NAP-1/IL-8 was present in significantly higher concentrations in the fluids of patients with ARDS compared with control subjects. There was a significant correlation between the percentage of neutrophils in the lavage fluids and the NAP-1/IL-8 concentration (r2 = 0.74). Furthermore, the NAP-1/IL-8 concentration of the pulmonary edema fluid was equivalent to the optimal concentration required to induce neutrophil chemotaxis in vitro. Although not all of the chemotactic activity of the edema fluid was removed by an anti-NAP-1/IL-8 affinity column, the data established that NAP-1/IL-8 is an important neutrophil chemotaxin in the airspaces of patients with ARDS. In addition, those patients with very high concentrations of NAP-1/IL-8 in their bronchoalveolar lavage fluids had a higher mortality rate than those patients with lower concentrations of NAP-1/IL-8. The correlation between NAP-1/IL-8 concentration and mortality is not paralleled by total protein concentration and mortality.

Adolescent↗

Accentuated complement activation in patient plasma during the adult respiratory distress syndrome: a potential mechanism for pulmonary inflammation.

The adult respiratory distress syndrome (ARDS) represents an acute inflammatory lung disorder, characterized by both refractory hypoxemia and a mortality rate approaching 95%. Researchers have proposed that activation of the complement (C) system may play a role in the development of the pulmonary inflammation associated with ARDS. The purpose of this investigation was to determine whether complement activation occurs to a greater extent in patients with ARDS than in patients without ARDS, thereby providing a potential mechanism for the acute inflammation seen in ARDS. In this study, we assessed plasma complement activation by measuring complement activation by-products: C1rC1s-C1 inhibitor complex and C3b-P complex, generated subsequent to activation of the classical and alternative pathways, respectively, and also the terminal complement complex, formed after activation of either the classical or alternative complement pathway. Multivariate discriminant analysis revealed that these three complement activation complexes could distinguish patients with ARDS from those without ARDS (p less than 0.04). Furthermore, these three complexes provided a more sensitive discriminator of ARDS than did plasma levels of C3a desarginine (p greater than 0.30), C5a desarginine (p greater than 0.41) and total hemolytic complement activity (CH50) (p greater than 0.72). We conclude that a temporal association exists between the complement activation and the development of ARDS. Therefore, we suggest that complement activation by-products be included in the armamentarium for ARDS.

Adult↗

[Pathophysiologic and therapeutic aspects of the adult respiratory distress syndrome (ARDS)].

Since the first characterization of the adult respiratory distress syndrome (ARDS), knowledge of its aetiology and pathogenesis has grown considerably. In spite of this, mortality remains up to 50 to 90%, particularly if multiple organ failure is present. Because no causative clinical therapy is available up to now, significant attention is given to preventive measures like early operative stabilisation of long bone fractures, or prophylaxis of nosocomial infections. After clinical manifestation of ARDS, treatment focuses on functional disturbances of the cardiopulmonary system and on the underlying disease. The aim of this symptomatic therapy is to ensure oxygen supply according to the organisms demand. It is still unknown, however, whether the mortality of patients with ARDS can be reduced by optimising the oxygen supply. In general, oxygen supply can be enhanced by improving pulmonary gas exchange, cardiac output and blood oxygen transport capacity. For practical use the therapy often ends up with a therapeutical dilemma: On one hand, the improvement of the pulmonary gas exchange by application of PEEP can be associated with a critical decline in cardiac output, particularly if the afterload of the right ventricle is elevated. On the other hand, to increase cardiac output, both volume replacement and vasodilators can severely affect pulmonary gas exchange if the alveolo-capillary permeability is increased and pulmonary hypoxic vasoconstriction is disturbed. Thus, oxygen supply can be optimised only via invasive monitoring of the cardiorespiratory system. Although still experimental, the most promising approaches seem to be pharmacological interventions directed at suppressing the formation and effects of various humoral and cellular mediators. An improved understanding of the inflammatory processes might provide new insights in the pathophysiology of ARDS and the related therapeutic interventions.

Humans↗

Bovine surfactant therapy for patients with acute respiratory distress syndrome.

Lung surfactant is deficient in patients with acute respiratory distress syndrome (ARDS). We performed a randomized, prospective, controlled, open-label clinical study of administration of a bovine surfactant to patients with ARDS to obtain preliminary information about its safety and efficacy. Patients received either surfactant by endotracheal instillation in addition to standard therapy or standard therapy only. Three different groups of patients receiving surfactant were studied: patients receiving up to eight doses of 50 mg phospholipids/kg, those receiving up to eight doses of 100 mg phospholipids/kg, and those receiving up to four doses of 100 mg phospholipids/kg. Outcome measures included ventilatory support parameters, arterial blood gases, organ system failures, bronchoalveolar lavage (BAL) analyses, immunologic analyses, survival, and adverse events during the 28-d study period. Fifty-nine study patients were evaluable; 43 in the surfactant group and 16 in the control group. The FI(O2) at 120 h after treatment began was significantly decreased only for patients who received up to four doses of 100 mg phospholipids/kg surfactant as compared with control patients (p = 0.011). Mortality in the same group of patients was 18.8%, as compared with 43.8% in the control group (p = 0.075). The surfactant instillation was generally well tolerated, and no safety concerns were identified. This pilot study presents preliminary evidence that surfactant might have therapeutic benefit for patients with ARDS, and provides rationale for further clinical study of this agent.

Adult↗

The relationship between cognitive performance and employment and health status in long-term survivors of the acute respiratory distress syndrome: results of an exploratory study.

Survivors of acute respiratory distress syndrome (ARDS) are at risk for long-lasting cognitive decline due to hypoxemia, sepsis and/or psychological sequelae associated with aggressive supportive care in the intensive care unit (ICU). We conducted an exploratory study to assess cognitive performance in long-term survivors of ARDS and to investigate how cognitive functioning is related to employment status and health-related quality of life (HRQOL). At median time of 6.0 years after ICU discharge, forty-six ARDS survivors were tested with SKT, a short cognitive performance test for assessing deficits of memory and attention. A measure of HRQOL (SF-36 Health Status Questionnaire) was also administered, and in a brief psychiatric interview, employment status was rated. 23.9% (n=11) of the patients showed cognitive impairments. However, no extreme and severe cognitive deficits were recorded. They primarily revealed low levels of cognitive function in various tasks assessing attention skills. Disability was found in 41.3% (n=19) of the patients. All ARDS survivors with cognitive deficits were disabled, whereas only 22.9% (n=8) of the cognitively not impaired patients gave evidence of disability. The SF-36 values of the ARDS survivors indicated impaired health status on seven out of eight domains when compared to normative population data. Patients with cognitive deficits described the lowest HRQOL with major limitations in the domains role-physical and social functioning when compared to patients without cognitive impairments. In conclusion, long-term ARDS survivors exhibit impaired health status and the presence of cognitive deficits is associated with disability and considerable impairments in HRQOL. More detailed psychiatric research is required to establish the etiology of these cognitive impairments.

Acute Disease↗

A genetic and statistical study of the respiratory distress syndrome.

The hospital records of 197 infants with the respiratory distress syndrome (RDS) were reviewed and the families of 111 of them subsequently contacted to obtain a family history. After correcting for biasis of ascertainment, the incidence of RDS among the full sibs was found to be between 12 and 19% depending on whether the individuals diagnosed as "possible RDS" were counted as affected. Among the low birth weight (LBW, less than or equal to 2.5 kg) and/or preterm (less than or equal to 37 weeks gestation) infants in the sibships, the incidence of RDS was 32-50%. Considering only sibs born after the probands yielded the empiric recurrence risk of 17--27% for all younger sibs and 39--67% for LBW/preterm younger sibs. The risk for maternal half-sibs was of about the same magnitude as that for full sibs, while the risk for paternal half-sibs was minimal. Among the LBW/preterm first cousins of probands, only the infants of maternal aunts showed an RDS incidence clearly higher than that in the general population. We think these data suggest a genetically determined maternal factor predisposing the infants of certain mothers to RDS. Other significant findings include: 1) an excess of males among the probands but a normal sex ratio among the sibs of the probands; 2) a decrease in mean birth weight and mean length of gestation for not only the probands but also their sibs; 3) a decrease in the mean parental ages at the birth of the probands; 4) a relative dearth of first-born and an excess of second-born infants among the probands; 5) an increased incidence of stillbirths in the sibships; 6) an increased number of probands born by cesarean section; and 7) a twin concordance of 75%.

Age Factors↗

Cardiopulmonary effects of permissive hypercapnia in the management of adult respiratory distress syndrome.

BACKGROUND: Despite numerous advances, the mortality from adult respiratory distress syndrome (ARDS) remains high. Traditional ventilator management in ARDS has been to maintain normal PaCO2 by positive pressure ventilation (PPV). However, high levels of PPV may worsen the lung injury by alveolar overdistension. Permissive hypercapnia (PHC) has been proposed as an alternative method of ventilation, but hypercapnia may affect the hemodynamics of a hyperdynamic, critically ill patient. The purpose of this study was to determine the effect of PHC on ventilator requirement, arterial oxygenation, and hemodynamic performance in patients with severe ARDS. METHODS: Ten men and 5 women with established ARDS (mean Murray lung injury score 3.42 +/- 0.1) were prospectively studied using an established protocol when the static pulmonary plateau pressure (Pplat) exceeded 40 cm H2O. The initial tidal volume (V(t)) was decreased to achieve a Pplat < 40 cm H2O or to a lower limit of 5 cc/kg. Arterial blood gas and hemodynamic data were obtained serially. RESULTS: The V(t) was reduced from 9.9 +/- 0.5 mL/kg to 7.7 +/- 0.5 mL/kg at 24 hours, p < 0.05. This reduction of V(t) produced a decrease in minute ventilation (Ve: 18.0 +/- 1.6 to 11.9 +/- 0.7 L/min, p < 0.05), peak airway pressure (PAP: 55 +/- 2 vs 45 +/- 3 cm H2O, p < 0.05), and Pplat (Pplat 45.4 +/- 1.5 vs. 36.7 +/- 1.9) at 24 hours. The PaCO2 rose from 37.9 +/- 1.3 to 56.7 +/- 3.0 mm Hg (p < 0.05), and the pH decreased from 7.41 +/- 0 to 7.31 +/- 0 (p < 0.05) at 24 hours. There were no significant changes in mean airway pressure, static compliance, arterial oxygenation, pulmonary vascular resistance, systemic vascular resistance, cardiac index, or systemic oxygen delivery and consumption. CONCLUSIONS: Permissive hypercapnia by V(t) reduction: (1) decreased Ve, PAP, and Pplat without a change in mean airway pressure, static compliance or arterial oxygenation; (2) caused a mild partially compensated acidosis; and (3) does not adversely affect pulmonary vascular resistance, systemic vascular resistance, cardiac index, or systemic oxygen delivery and consumption.

Adolescent↗