Perioperative fluid management for major elective surgery.

BACKGROUND: Adequate fluid balance before, during and after surgery may reduce morbidity. This review examines current concepts surrounding fluid management in major elective surgery. METHOD: A narrative review was undertaken following a PubMed search for English language reports published before July 2019 using the terms 'surgery', 'fluids', 'fluid therapy', 'colloids', 'crystalloids', 'albumin', 'starch', 'saline', 'gelatin' and 'goal directed therapy'. Additional reports were identified by examining the reference lists of selected articles. RESULTS: Fluid therapy is a cornerstone of the haemodynamic management of patients undergoing major elective surgery. Both fluid overload and hypovolaemia are deleterious during the perioperative phase. Zero-balance fluid therapy should be aimed for. In high-risk patients, individualized haemodynamic management should be titrated through the use of goal-directed therapy. The optimal type of fluid to be administered during major surgery remains to be determined. CONCLUSION: Perioperative fluid management is a key challenge during major surgery. Individualized volume optimization by means of goal-directed therapy is warranted during high-risk surgery. In most patients, balanced crystalloids are the first choice of fluids to be used in the operating theatre. Additional research on the optimal type of fluid for use during major surgery is needed.

ANTECEDENTES: Un equilibrio de líquido adecuado antes, durante y después de la cirugía puede reducir la morbilidad. Esta revisión presenta los conceptos actuales del manejo de líquidos en cirugía mayor electiva. MÉTODOS: Se realizó una revisión descriptiva tras llevar a cabo una búsqueda en PubMed de artículos publicados en inglés antes de julio 2019, utilizando los términos 'cirugía ' (surgery), 'líquidos' (fluids), `fluidoterapia` (fluid therapy), 'coloides' (colloids), 'cristaloides' (crystalloids), 'albúmina' (albumin), 'hidroxietil-almidón' (starch), 'salino' (saline), 'gelatina' (gelatin) y 'terapia dirigida por objetivo' (goald directed therapy). Se identificaron artículos adicionales a través de la lista de referencias bibliográficas de los artículos seleccionados. RESULTADOS: El tratamiento con líquidos constituye la piedra angular del manejo hemodinámico de los pacientes sometidos a cirugía mayor electiva. Tanto la sobrecarga de líquidos como la hipovolemia son perjudiciales durante el periodo perioperatorio. El tratamiento de líquidos con balance cero debe considerarse el objetivo. En pacientes de alto riesgo, el manejo hemodinámico personalizado se debe ajustar mediante la utilización del tratamiento dirigido por objetivos. El tipo óptimo de líquido que debe ser administrado durante la cirugía mayor todavía no se ha determinado. CONCLUSIÓN: El manejo perioperatorio de líquidos es un desafío clave durante la cirugía mayor. La optimización del volumen individualizado a través de un tratamiento dirigido por objetivos está justificada durante la cirugía de alto riesgo. En la mayoría de los casos, la administración equilibrada de cristaloides es la primera fluidoterapia de elección en el quirófano. Se necesitan más investigaciones sobre el tipo de líquidos más adecuado para utilizar durante la cirugía mayor.

Procedure volume is one determinant of centre effect in mechanically ventilated patients.

Survival rates vary significantly between intensive care units, most notably in patients requiring mechanical ventilation (MV). The present study sought to estimate the effect of hospital MV volume on hospital mortality. We included 179,197 consecutive patients who received mechanical ventilation in 294 hospitals. Multivariate logistic regression models with random intercepts were used to estimate the effect of annual MV volume in each hospital, adjusting for differences in severity of illness and case mix. Median annual MV volume was 162 patients (interquartile range 99-282). Hospital mortality in MV patients was 31.4% overall, 40.8% in the lowest annual volume quartile and 28.2% in the highest quartile. After adjustment for severity of illness, age, diagnosis and organ failure, higher MV volume was associated with significantly lower hospital mortality among MV patients (OR 0.9985 per 10 additional patients, 95% CI 0.9978-0.9992; p = 0.0001). A significant centre effect on hospital mortality persisted after adjustment for volume effect (p < 0.0001). Our study demonstrated higher hospital MV volume to be independently associated with increased survival among MV patients. Significant differences in outcomes persisted between centres after adjustment for hospital MV volume, supporting a role for other significant determinants of the centre effect.

Patients requiring pediatric palliative care for advanced heart disease in France: A descriptive study.

INTRODUCTION: Pediatric palliative care (PPC) teams address unmet needs and improve the quality of life of patients with life-limiting conditions across pediatric subspecialties. However, little is known about the timing, reasons, and nature of PPC team interventions in advanced heart diseases (AHD). OBJECTIVES: Here we describe how, when, and why PPC teams interact with referred teams of children suffering from AHD. METHODS: We conducted a retrospective nationwide survey among PPC teams in France. All patients referred to participating PPC teams for a cardiologic disease in 2019 were studied. RESULTS: Among six PPC teams, 18 patients with AHD had a PPC consultation in 2019. Six of these patients had cardiomyopathy and 12 had congenital heart disease (CHD). The median age at referral was 0.9 months for CHD and 72 months for cardiomyopathy. An antenatal diagnosis had been made for six families with CHD, and two of them were referred to PPC before birth allowing for a prenatal palliative care plan. The main reason for referral was ethical considerations (50%) followed by organization for home-based palliative care (28%). PPC teams participated in ethical discussions when asked to but also provided family support (12/18), home-based PPC (9/18), coordination of care (5/18), support of the referred team (4/18), and symptoms management (3/18) CONCLUSION: The main reason for referral to PPC was ethical considerations, but PPC interventions followed a holistic model of care. Prospective outcomes measurement and partnerships should be further developed.

Hemorrhage increases cytokine expression in lung mononuclear cells in mice: involvement of catecholamines in nuclear factor-kappaB regulation and cytokine expression.

The expression of proinflammatory and immunoregulatory cytokines rapidly increases in the lungs after hemorrhage, and such alterations contribute to the frequent development of acute inflammatory lung injury in this setting. Blood loss also produces elevations in catecholamine concentrations in the pulmonary and systemic circulation. In the present experiments, we used alpha- and beta-adrenergic receptor blockade to examine in vivo interactions between hemorrhage-induced adrenergic stimulation and pulmonary cytokine expression. Treatment of mice with the alpha-adrenergic receptor antagonist phentolamine prevented not only the elevation in mRNA levels of IL-1beta, TNF-alpha, and TGF-beta1, the increase in IL-1beta protein, but also the activation of nuclear factor (NF)-KB and cyclic AMP response element binding protein, which occurred in lung cells of untreated animals during the first hour after hemorrhage. In contrast, treatment before hemorrhage with the beta-adrenergic receptor antagonist propranolol was associated with increases in mRNA levels for IL-1beta, TNF-alpha, and TGF-beta1, which were greater than those present in untreated hemorrhaged mice, and did not prevent hemorrhage-associated increases in lung IL-1beta protein. Treatment with propranolol prevented hemorrhage-induced phosphorylation of cyclic AMP response element binding protein, but increased hemorrhage-associated activation of NF-KB. These results demonstrate that hemorrhage initially increases pulmonary cytokine expression through alpha- but not beta-adrenergic stimulation, and suggest that such alpha-adrenergic-mediated effects occur through activation of the transcriptional regulatory factor NF-kappaB.

Erythrocyte spermine levels: a prognostic parameter in childhood common acute lymphoblastic leukemia.

Polyamines have been implicated to play a role in cell proliferation and in cancer development. Ninety percent of the circulating spermidine (Spd) and spermine (Spm) are transported by red blood cells (RBC). RBC Spd and Spm levels were prospectively determined in 63 unselected children with common acute lymphoblastic leukemia. The Spm and Spd levels were not correlated with white blood cell (WBC) count. On the basis of the polyamine levels it was possible to discriminate four groups with P< 10(-3). In C1, C2, C3 and C4 group the Spm level was respectively 90 (39-597), 3.75 (1-7.45), 9.95 (2.9-12.6) and 17(6.3-33.8). The probability of relapse-free survival (RFS) of the 58 children who entered complete remission was 55% +/- 9. For the groups C1 (n = 6), C2 (n = 16), C3 (n = 21) and C4 (n= 15) groups, the RFS was 25% +/- 20, 73% +/- 12, 73% +/- 13 and 32% +/- 13 respectively. For children with Spm levels <13/> or = 13nmol/8 x 10(9) RBC, event-free survival (EFS) was 54% +/- 11/33% +/- 10 and RFS was 64% +/- 12/38% +/- 11 respectively (P < 0.03, P < 0.005). Our clinical study shows clearly that an RBC spermine level could be used as parameter of prognosis at the time of diagnosis, particularly for patients with intermediary WBC count.

Deletion or lack of expression of CDKN2 (CDK4I/MTS1/INK4A) and MTS2 (INK4B) in acute lymphoblastic leukemia cell lines reflects the phenotype of the uncultured primary leukemia cells.

The CDKN2 gene has been recently localized to a chromosomal region found to be deleted in leukemias and solid tumors. CDKN2 encodes a 16 kDa protein product (p16INK4A), which functions as a specific inhibitor or the cyclin-dependent kinases 4 and 6. There have been many reports indicating a higher frequency of deletions of the CDKN2 gene in a variety of tumor cell lines, in comparison to primary tumors. These studies raise the possibility that deletions of CDKN2 may be a rare event in primary tumors, and in fact arise in vitro, during the establishment of permanent cell lines. To address this issue, we determined whether the CDKN2 gene deletions found in acute lymphoblastic leukemia (ALL) cell lines are also detected in the primary leukemia samples. Eleven cell lines were identified which had available frozen primary samples of their original leukemic tissue. Five out of 11 of these cell lines, as well as their primary samples had homozygous CDKN2 deletions. The remaining six cell lines and their primary samples retained at least one copy of the CDKN2 gene. Of the six CDKN2+ cell lines, five expressed CDKN2 mRNA, but only one of these expressed the p16 protein product (as did its primary sample). Our results indicate that CDKN2 deletions present in the studied ALL cell lines arose in the primary leukemic cells, and not during cell line establishment or prolonged in vitro culture.

Long-term-impaired expression of nuclear factor-kappa B and I kappa B alpha in peripheral blood mononuclear cells of trauma patients.

Nuclear factor (NF)-kappa B expression and dimer characteristics were studied in peripheral blood mononuclear cells (PBMCs) of major-trauma patients and healthy controls. Analysis of PBMCs on days 1, 3, 5, and 10 after trauma revealed that expression of both p65p50 heterodimers and p50p50 homodimers was significantly reduced compared with that in controls. In vitro lipopolysaccharide (LPS) stimulation of PBMCs induced NF-kappa B translocation. However, throughout the survey, p65p50 activation remained significantly lower in trauma patients than in controls. After LPS stimulation in vitro, the p65p50/p50p50 ratio was significantly lower in PBMCs from trauma patients than from healthy controls. The ex vivo expression of I kappa B alpha was higher in PBMCs of controls than of trauma patients. LPS did not induce I kappa B expression in PBMCs from trauma patients, but strong induction was obtained with staphylococci, suggesting that this defect is not universal and depends on the nature of the activating signal. Although no direct correlation was found between levels of interleukin-10 or transforming growth factor-beta and NF-kappa B, these immunosuppressive cytokines were significantly elevated in trauma patients by 10 days after admission. The long-term low-basal and LPS-induced nuclear translocation of NF-kappa B recalled long-term immunoparalysis observed in patients with severe inflammatory stress such as trauma.

[Differential modulation of TLR2 and TLR4-induced TNF production by murin haemorrhagic shock]. / Modulation différentielle des effets de la stimulation des récepteurs Toll-like 2 et 4 par l'état de choc hémorragique.

OBJECTIVE: To investigate the influence of haemorrhagic shock in mice on ex vivo TNF production by whole blood cells (WBC) stimulated through Toll-like receptors (TLR) 4 and 2. STUDY DESIGN AND ANIMALS: Experimental study using BALB/c male mice. METHODS: Haemorrhage (0,026+/-0,003 ml/g) by transparietal cardiac puncture under general anaesthesia. Measurement of left intraventricular pressure through a direct subcostal cardiac puncture. Possible restitution of shed blood volume (SBV) in retroorbital venous plexus, 60 minutes following haemorrhage. Lethal exsanguination 120 minutes following general anaesthesia (Control group), cardiac puncture (Sham group), blood sample (Haemorrhage group), or 60 minutes following SBV retransfusion (SBV group). Cultures (24 hours) of whole blood from the exsanguination, alone or with Escherichia coli endotoxin (LPS, TLR 4) or with heat-killed Staphylococcus aureus Cowan (SAC, TLR 2). Assessment of TNF levels in the cultures supernatant (Elisa). RESULTS: Hemorrhage (approximately 30% of calculated blood volume) resulted in arterial hypotension (-50%) which was reversed by SBV retransfusion. TNF production by LPS-stimulated WBC was reduced by haemorrhage (approximately -50%) with or without SBV retransfusion. TNF production by SAC-stimulated WBC remained unchanged. CONCLUSION: The reduction of proinflammatory cytokines production by WBC stimulated with pathogen-associated molecular patterns is not a generalized phenomenon following murin haemorrhagic shock. It depends on the used stimulus and studied signalling pathways.

Growth inhibition of B-cell precursor acute lymphoblastic leukemia cell lines by monocytes: a role for prostaglandin E2.

Leukemic cell lines have proven invaluable in the molecular analysis of recurring chromosomal translocations but the optimal methods for leukemia cell line establishment are unknown. During in vitro culture, most B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells die within 1 week at least partially mediated by inhibitors elaborated by peripheral blood mononuclear cells (PB MNCs) present within the leukemia sample. In experiments reported here, cyclooxygenase inhibitors (indomethacin and meclofenamic acid) blocked the PB MNC-mediated inhibition of BCP-ALL proliferation. Also, prostaglandin E2 (PGE2) was detected in supernatants from PB MNC cultures. When PGE2 was mixed directly with BCP-ALL cells, proliferation decreased significantly. Under the culture conditions used, PB MNCs secreted PGE2 which appears to be one of the major inhibitors of BCP-ALL growth in vitro.

NF-kappaB regulatory mechanisms in alveolar macrophages from patients with acute respiratory distress syndrome.

Activation of the nuclear regulatory factor NF-kappaB occurs in the lungs of patients with the acute respiratory distress syndrome (ARDS) and may contribute to the increased expression of immunoregulatory cytokines and other proinflammatory mediators in this setting. Because of the important role that NF-kappaB activation appears to play in the development of acute lung injury, we examined cytoplasmic and nuclear NF-kapppaB counterregulatory mechanisms, involving IkappaB proteins, in alveolar macrophages obtained from 7 control patients without lung injury and 11 patients with established ARDS. Cytoplasmic levels of the NF-kappaB subunits p50, p65, and c-Rel were significantly decreased in alveolar macrophages from patients with ARDS, consistent with enhanced migration of liberated NF-kappaB dimers from the cytoplasm to the nucleus. Cytoplasmic and nuclear levels of IkappaBalpha were not significantly altered in alveolar macrophages from patients with established ARDS, compared with controls. In contrast, nuclear levels of Bcl-3 were significantly decreased in patients with ARDS compared with controls (P = 0.02). No IkappaBgamma, IkappaBbeta, or p105 proteins were detected in the cytoplasm of alveolar macrophages from control patients or patients with ARDS. The presence of activated NF-kappaB in alveolar macrophages from patients with established ARDS implies the presence of an ongoing stimulus for NF-kappaB activation. In this setting, appropriate counterregulatory mechanisms to normalize nuclear levels of NF-kappaB and to suppress NF-kappaB-mediated transcription, such as increased cytoplasmic and nuclear IkappaBalpha levels or decreased Bcl-3 levels, appeared to be induced. Nevertheless, even though counterregulatory mechanisms to NF-kappaB activation are activated in lung macrophages of patients with ARDS, NF-kappaB remains activated. These results suggest that fundamental abnormalities in transcriptional mechanisms involving NF-kappaB and important in the inflammatory response occur in the lungs of patients with ARDS.

Is the duration of mechanical ventilation predictable?

BACKGROUND: Prolonged mechanical ventilation (MV) is associated with high morbidity, mortality, and cost. However, few and limited data are available on the prediction of duration of MV. We conducted an observational cohort study to seek predictive criteria. METHODS: The study was performed in a surgical ICU (SICU) in a university hospital. One hundred ninety-five consecutive unselected patients and 203 episodes of MV were prospectively analyzed to determine if clinical features, physiologic parameters, or multifactor scoring systems, at the time of admission or intubation, could be used as predictors of MV > or = 15 days. A univariate statistical analysis and a multiple logistic regression were used. A prospective validation study was then conducted to determine the accuracy of the results. RESULTS: (1) Univariate statistical analysis indicated that SICU length of stay, emergent endotracheal intubation as opposed to elective intubation, indication for MV, sepsis score at the time of admission and intubation, lung injury score (LIS) at the time of admission and intubation, number of organ system failures at the time of admission and intubation, and serum albumin concentration were significantly different between the two groups. (2) Only the circumstances (emergency) of endotracheal intubation (odds ratio [OR]=3.5, p=0.02) and the LIS (OR=3.7, p=0.004) independently predicted a duration of endotracheal intubation > or = 15 days. One hundred twenty-eight consecutive patients requiring emergent intubation and MV were included in the prospective validation. The accuracy of the LIS > or = 1 used to predict MV > or = 15 days was as follows: sensitivity=0.88; specificity=0.28; positive predictive value=0.24; negative predictive value=0.91. CONCLUSION: Low incidence of MV > or = 15 days was observed (13% and 20%, respectively, in observational cohort study and validation study) in unselected SICU patients. LIS > or = 1 at the time of intubation provides excellent negative predictive value (0.93 and 0.91) of duration of MV > or = 15 days. These data suggest that tracheotomy should not be considered for patients with LIS < 1.

Severe community-acquired pneumonia. Etiology, epidemiology, and prognosis factors. French Study Group for Community-Acquired Pneumonia in the Intensive Care Unit.

A prospective study of 132 patients with severe community-acquired pneumonia (CAP) treated in the ICU was carried out to determine the causative agents, the value of the clinical, biological, and radiologic features in predicting the etiology, and to define prognostic factors. The study group included 98 men and 34 women (mean age: 58 +/- 18 years). The most frequent underlying condition was COPD (51 patients, 39 percent). On admission, 35 patients were in shock, 71 were mentally confused, and 81 (61 percent) required mechanical ventilation during their hospitalization. The clinical, laboratory, and radiologic parameters were of little value for predicting the etiology in patients with severe CAP. An etiologic diagnosis was made in 95 (72 percent) patients. The most frequent pathogens were Streptococcus pneumoniae (43 cases [45 percent]), Gram-negative bacilli (14 cases [15 percent]), and Haemophilus influenzae (14 cases [15 percent]) Mortality was 24 percent. It was significantly associated with a age more than 60 years, septic shock, impairment of alertness, mechanical ventilation requirement, bacteremic pneumonia, and S pneumoniae or Enterobacteriaceae as the causes of the pneumonia. Recommendations for antibiotic chemotherapy in patients with severe CAP admitted to the ICU are included.

Erythrocyte polyamine levels: an indication of successful engraftment of bone marrow in children.

We studied the evolution of erythrocyte polyamine levels after 17 autologous bone marrow transplants (BMT) in 16 children with malignant diseases. We found that the time to the end of aplasia (0.5 x 10(9) granulocytes per liter) could be divided into 2 distinct periods. The first is characterized by low erythrocyte spermidine (Spd) and spermine (Spm) levels; the second is characterized by normal levels of polyamines. Spd and Spm levels were correlated (r = 0.74) during the second period, but not during the first period or in the control group. Furthermore, the time when Spd concentration was > or = 7 nmol/8 x 10(9) erythrocytes (19 +/- 7) was correlated (r = 0.64) with the advent of end of aplasia (30 +/- 10). We found no correlation between the numbers of CFU-GM and duration of aplasia levels or the duration of period A. The establishment of normal erythrocyte spermidine levels is the earliest index of successful marrow engraftment.

Accuracy of a composite score using daily SAPS II and LOD scores for predicting hospital mortality in ICU patients hospitalized for more than 72 h.

UNLABELLED: In most databases used to build general severity scores the median duration of intensive care unit (ICU) stay is less than 3 days. Consequently, these scores are not the most appropriate tools for measuring prognosis in studies dealing with ICU patients hospitalized for more than 72 h. PURPOSE: To develop a new prognostic model based on a general severity score (SAPS II), an organ dysfunction score (LOD) and evolution of both scores during the first 3 days of ICU stay. DESIGN: Prospective multicenter study. SETTING: Twenty-eight intensive care units (ICUs) in France. PATIENTS: A training data-set was created with four ICUs during an 18-month period (893 patients). Seventy percent of the patients were medical (628) aged 66 years. The median SAPS II was 38. The ICU and hospital mortality rates were 22.7% and 30%, respectively. Forty-seven percent (420 patients) were transferred from hospital wards. In this population, the calibration (Hosmer-Lemeshow chi-square: 37.4, P = 0.001) and the discrimination [area under the ROC curves: 0.744 (95 % CI: 0.714-0.773)] of the original SAPS II were relatively poor. A validation data set was created with a random panel of 24 French ICUs during March 1999 (312 patients). MEASUREMENTS AND MAIN RESULTS: The LOD and SAPS II scores were calculated during the first (SAPS1, LOD1), second (SAPS2, LOD2), and third (SAPS3, LOD3) calendar days. The LOD and SAPS scores alterations were assigned the value "1" when scores increased with time and "0" otherwise. A multivariable logistic regression model was used to select variables measured during the first three calendar days, and independently associated with death. Selected variables were: SAPS II at admission [OR: 1.04 (95 % CI: 1.027-1.053) per point], LOD [OR: 1.16 (95 % CI: 1.085-1.253) per point], transfer from ward [OR: 1.74 (95 % CI: 1.25-2.42)], as well as SAPS3-SAPS2 alterations [OR: 1.516 (95 % CI: 1.04-2.22)], and LOD3-LOD2 alterations [OR: 2.00 (95 % CI: 1.29-3.11)]. The final model has good calibration and discrimination properties in the training data set [area under the ROC curve: 0.794 (95 % CI: 0.766-0.820), Hosmer-Lemeshow C statistic: 5.56, P = 0.7]. In the validation data set, the model maintained good accuracy [area under the ROC curve: 0.826 (95 % CI: 0.780-0.867), Hosmer-Lemeshow C statistic: 7.14, P = 0.5]. CONCLUSIONS: The new model using SAPS II and LOD and their evolution during the first calendar days has good discrimination and calibration properties. We propose its use for benchmarking and evaluating the over-risk of death associated with ICU-acquired nosocomial infections.

Analysis of the side effects of tianeptine.

The evaluation of clinical and paraclinical safety of tianeptine was performed in (a) clinical pharmacology studies assessing night sleep EEG organization; electrocardiographic stability by continuous 24-h recordings (Holter's method); ocular tonus in patients with stabilized glaucoma; salivary flow; prolactin secretion; photodynamic dermatologic reactions; cerebral electrical activity; hematologic, hepatic, renal and main metabolic parameters; separately, withdrawal phenomena and addictive potential were searched for in drug addicts; (b) double-blind controlled studies versus reference compounds. The results confirm that the therapeutic safety of tianeptine is satisfactory with respect to clinical side effects and paraclinical parameters. Tianeptine does not induce sedation and thus does not disturb the recovery of active life. It does not induce anticholinergic effects (dry mouth, constipation, etc.), even in elderly subjects. It is devoid of heart and blood pressure side effects including postural hypotension tachycardia, ECG abnormalities, and especially atrioventricular or intraventricular conduction disorders. Moreover, tianeptine does not disturb the hematologic, renal, hepatic parameters, even in alcoholic patients in the detoxification period. It does not induce physical or psychological signs of dependence when discontinued, even in alcoholic patients or drug addicts. No abuse of tianeptine and no tolerance were noted in detoxified opiate addicts.

Efficiency of inhaled nitric oxide as rescue therapy during severe ARDS: survival and factors associated with the first response.

PURPOSE: The purpose of this study was to determine if the response to inhaled nitric oxide (NO) as salvage therapy is an independent factor for survival in adult respiratory distress syndrome (ARDS) patients and to identify the factors that predict the response to inhaled NO during ARDS. MATERIALS AND METHODS: This was a multicenter, 2-year retrospective, clinical study in five university surgical or medical intensive care units, including all consecutive patients with ARDS in whom inhaled NO was tried. Clinical data (medical history, diagnoses), general severity scores (SAPS II, OSF), biological data, radiological and hemodynamic data at admission, at the beginning of the ARDS, and under treatment with inhaled NO were recorded. The NO response was defined as the variation of PaO2/Fio2 ratio before initiation and after 30 minutes of NO inhalation (VarPaO2/FiO2). RESULTS: Ninety-three patients aged 49 +/- 18 years were studied. Mean SAPS II was 45 +/- 16. Before the beginning of inhaled NO, PaO2/Fio2 ratio was 95 +/- 53 mm Hg and lung injury score 2.7 + 0.3. VarPao2/Fio2 when NO was started (11 +/- 4 ppm) was 26 +/- 44.5 mm Hg (median 17 mm Hg). Intensive care unit mortality was 74%. None of the parameters studied were predictors of response to inhaled NO, although there was a tendency for the youngest patients with the more severe hypoxemia to have a better response. Response to first inhaled NO test (VarPaO2/FiO2) was univariately associated with survival (Survivors: 45 +/- 44 mm Hg vs. Nonsurvivors: 20 +/- 43 mm Hg, P = .01), but this difference disappeared after adjusting for other prognostic factors (P = .16) selected by multivariate analysis. Finally, inhaled NO was continued for more than 1 day for 75 patients, and definitively stopped for 18 patients. Intensive care unit mortality (73% vs. 78%) was not different between these groups (P = .25, Log-rank test). CONCLUSIONS: We conclude that (1) efficacy of inhaled NO in improving oxygenation was moderate and difficult to predict, (2) response to first NO inhalation was not associated with prognosis, and (3) treatment of the most severe ARDS patients with inhaled NO did not influenced their intensive care unit survival.

Molecular diagnosis of Duchenne muscular dystrophy by use of a conformational polymorphism in the absence of DNA from an affected boy.

We report the molecular diagnosis of Duchenne muscular dystrophy (DMD) in an extended pedigree by use of a conformational polymorphism detected by the SSCP method, which allowed direct prenatal diagnosis and carrier detection while no DNA from an affected boy was available.

Proximal fractures of the fifth metacarpal: a retrospective analysis of 25 operated cases.

The clinical and radiological outcomes of 25 surgically treated fractures of the proximal third of the fifth metacarpal were retrospectively analysed. Many different methods of osteosynthesis were used. At follow-up after a mean of 3.3 years, 15 of 25 patients had no pain. Most patients regained a nearly full range of motion in the adjacent joints and more than 90% of the contralateral grip strength. X-ray signs of degenerative arthritis in the metacarpohamate joint were observed in 10 of 25 patients. Pain was found to be directly correlated with the presence of degenerative changes.

[Caudal block in children: analgesia and respiratory effect of the combination bupivacaine-fentanyl]. / Bloc caudal chez l'enfant: analgésie et effets respiratoires de l'association bupivacaïne-fentanyl.

A study of the duration of analgesia and of the respiratory response to hypercapnia was carried out in 14 children who had had a caudal block with either bupivacaine alone (group B) or combined with fentanyl (Group B+F). Fourteen ASA I or II 5 to 10-year-old children undergoing genital and urinary surgery were included. They were not premedicated. At first, general anaesthesia was induced with halothane and nitrous oxide in oxygen. Thereafter, caudal anaesthesia was then carried out with 1 ml.kg-1 of 0.25% bupivacaine with adrenaline 1 in 200,000. Group B+F patients were also given 1 microgram.kg-1 of fentanyl in 1 ml of normal saline, and those in Group B 1 ml of normal saline. The level of sensory loss on leaving the operating theatre as well as the duration of motor paralysis were monitored. Postoperative pain was scored with Hannalah and Broadman's score (0 to 10) 2, 4, 8 and 24 h after the caudal block. Respiratory rate (fR), tidal volume (VT) and minute ventilation (VE) were assessed 10 min before induction of general anaesthesia, and 30, 60 and 120 min after the caudal anaesthesia. Petco2 was also measured before induction of general anaesthesia, and 60 and 120 min after caudal anaesthesia; at the same times, the ventilatory response to hypercapnia was assessed using Read's method with a Douglas bag containing 7% CO2 and 93% O2.(ABSTRACT TRUNCATED AT 250 WORDS)

[Gas gangrene after aseptic orthopedic surgery]. / Gangrène gazeuse après chirurgie orthopédique aseptique.

Gas gangrene following scheduled orthopedic surgery is not uncommon. In order to assess its frequency and prognosis, identify possible predisposing factors and suggest preventive measures, we reviewed the records of 22 patients (14 males and 8 females, mean age 40 +/- 20 years) admitted between 1969 and 1987 who developed gas gangrene in the wake of orthopedic surgery. In all cases the lower limbs were the site of operation: the knee in 9, the hip in 4, the femur in 4 and the leg in 5 cases. Surgical procedures included on-site foreign material in 19 cases, pneumatic tourniquet in 6 and prolonged vascular stretch in 9. Infection was diagnosed within 1.4 +/- 1.1 days of surgery; local signs, especially crepitants and pain, were prominent for the diagnosis. Pathologic findings consisted of myonecrosis in 18 patients and cellulitis in 4. Local bacteriological studies, carried out in 19 patients, yielded organisms in 14, including 12 with Clostridia perfringens. Four patients (one despite surgical treatment) died within 24 hours of admission. The remainder were treated with a combination of surgery, antimicrobial therapy (18) and hyperbaric oxygen (17). Subsequently, 13 patients had severe functional disability, while 5 recovered without sequelae. In view of the poor prognosis of gas gangrene, several preventive measures are suggested during aseptic surgery of the lower limbs. Careful skin preparation, cleaning of the anal region and short-term prophylactic antibiotic therapy with cefamandole or amoxycillin-clavulanic acid, are among them.