Protein C concentrate and recombinant tissue plasminogen activator in meningococcal septic shock.
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Biomedical subjects
Publications and source records attributed to R Cremer.
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Meningococcal septic shock (MSS) has high mortality and morbidity rates. In addition to the traditional prompt antibiotics and respiratory and circulatory support, new treatment strategies have been proposed. AGAINST THE INFLAMMATORY CASCADE: Immunotherapy, such as antiserum to Escherichia coli J5 and human antilipid A monoclonal antibodies/centoxin (HA-1A), did not significantly alter the mortality rate of MSS; we are awaiting the results of the bactericidal/permeability-increasing protein multicenter trial. Two series reported the effects of hemofiltration and hemodiafiltration in MSS, but the true benefits remain unknown. TO TREAT HEMOSTATIC ABNORMALITIES: In MSS, heparin is still controversial and antithrombin concentrate use has been reported in only one child. Several case reports on protein C and recombinant tissue plasminogen activator have been published; the efficacy (improvement in shock and organ dysfunction and reduction in amputation rate) and safety (intracerebral hemorrhage with recombinant tissue plasminogen activator) of these treatments need further evaluation. Blood and plasma exchange appear to be safe and are supposed to reduce mortality, but it is difficult to draw firm conclusions from published studies. Finally, local application of medicinal leeches has been reported to improve purpuric lesions. TO INDUCE VASODILATION: Prostacyclin, or epoprostenol, infusion, sodium nitroprussiate infusion, sympathetic blockade, and topical nitroglycerin have been reported to improve distal perfusion; however, these reports are all anecdotal. OTHER STRATEGIES: Improvement in limb perfusion was achieved after hyperbaric oxygenation in patients with purpura fulminans caused by different pathogens. Most authors recommend monitoring of compartment pressures and performing fasciotomy as indicated. Finally, extracorporeal membrane oxygenation was recently proposed to support seven children with intractable MSS. CONCLUSIONS: There is no proof that unconventional treatments have a significant impact on outcome in MSS; prospective multicenter trials are needed. At present, early recognition of meningococcal sepsis and appropriate treatment seem to be the optimal methods of improving outcome. Efforts to find an effective meningococcal vaccine must be continued.
We applied to 20 paralyzed ventilated children (0.15 to 14.3 yr, six with acute respiratory distress syndrome [ARDS]) the low-flow inflation (LFI) technique providing quasi-static volume-pressure (V-P) curves and compared the assessment of overdistension (OD) on dynamic and LFI (reference) inspiratory V-P curves. Dynamic curves were obtained at the airway opening during regular constant flow ventilation (Servo 300). Then LFI curves were obtained. Two analyses were performed: First, the nonlinear coefficient c of a second order polynomial equation (SOPE) fitted to dynamic data obtained during constant flow was compared with the c of SOPE fitted to LFI curve (within tidal volume [VT]). Second, the dynamic C20/C (ratio of compliance of the last 20% of the curve (C20) to total compliance [C]) was compared with the determination of the upper inflection point (UIP) on the LFI curve. OD was defined as a negative value of c, a C20/C < 0.80, an UIP included within the VT range for that child during regular ventilation. Using LFI V-P curves as reference, SOPE offered a better detection of OD than dynamic C20/C or the determination of the UIP by graphical means. Indeed the first analysis showed a substantial agreement (kappa 0.75) between dynamic c and LFI c detection of OD whereas the second analysis showed a poor agreement (kappa 0.22) between C20/ C and LFI detection of the UIP. In conclusion, quasi-static V-P curves can easily be obtained in children with the LFI technique. SOPE offers a good detection of OD on dynamic and LFI V-P curves but the C20/C index seems to be an inadequate measure of OD.
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UNLABELLED: More than 10% of children surviving septic shock with purpura have skin necrosis or limb ischaemia (SNLI.). Among 44 children consecutively admitted to our pediatric intensive care unit, 35 (80%) survived, 6 of them (17%) developed SNLI (defined as the need of a surgical procedure). Two timed haemostasis measurements included the determination of coagulation factors, protein C (PC), protein S (PS), C4b binding protein (C4bBP), antithrombin (AT), and plasminogen activator inhibitor 1 (PAI-1). Two severity scores and CRP levels were determined at admission. Children with SNLI and without SNLI were compared. On admission, severity scores, and AT, PC, PS, C4bBP levels were similar in both groups with and without SNLI. Prothrombin time (23% vs 34%; P < 0.01), factor VII+X (20% vs 31%; P = 0.05) and factor VII (0% vs 19%; P < 0.01) were lower in the group with SNLI. The 2nd sample showed no difference between the two groups. Kinetics of haemostatic abnormalities were no different between the two groups. CONCLUSION: In this series, the only difference between the two groups was lower factor VII levels in children with skin necrosis or limb ischaemia. This suggests the benefit of tissue factor pathway inhibitor administration as an adjunctive therapy to prevent skin necrosis or limb ischaemia. Further studies including more children are needed to determine the potential effects of treatments such as protein C, antithrombin, and plasminogen activator inhibitor antibody administration, and to advocate tissue factor pathway inhibitor in preventing skin necrosis or limb ischaemia.
CASE REPORT: A 13 year old boy had a seven day history of chest pain and dyspnea. His right hemithorax was immobile with abolished breathing sounds. Initial chest X-ray revealed a right tension pneumothorax. A chest tube was inserted and the right lung re-expanded. However, despite two intrapleural injections of tetracyclin, the pneumothorax reappeared. Lung CT scan showed an intraparechymal cyst in the posterior part of the right upper lobe. Lobectomy was performed and histological study confirmed the diagnosis of type I cystic adenomatoid malformation of the lung. Two months after surgery, clinical and radiological examinations were normal. CONCLUSION: Spontaneous pneumothorax, as the initial manifestation of cystic adenomatoid malformation of the lung, is rare (three cases reported in children beyond the neonatal period, and two in adults). CT scan features correlate well with the pathologic features. Because of the risk of recurrent pulmonary infections and malignancy change, removal of the cystic lesions is advisable.
BACKGROUND: In industrialized countries where immunization against Haemophilus influenzae b (Hib) is largely used, the incidence of invasive Hib infections has dramatically decreased. The aim of this study was to analyse the impact of immunization against Hib on the incidence of invasive Hib infections in the Nord-Pas-de-Calais area in France. PATIENTS AND METHODS: This retrospective multicenter study enrolled 11 of the 18 hospitals in the Nord-Pas-de-Calais area, comparing two periods: 1991-1993 (before immunization), and 1994-1996 (during immunization). All children less than 60 months of age and having an invasive Hib infection were included. The Pasteur-Mérieux Company was asked to provide the number of vaccines sold in the Nord-Pas-de-Calais area during the study period. RESULTS: The number of vaccines sold in 1992 was 56,208; this reached 189,173 in 1996, corresponding to an immunization ratio higher than 90%. One hundred and two children representing 155 invasive Hib infections were studied. The annual incidence was 42 during the first period (meningitis: 18.6; septicemia: 14.6; epiglottitis: 5.6), and nine (meningitis: 5; septicemia: 2.6; epiglottitis: 0.3) during the second period, that is a 78% decrease. CONCLUSION: These results confirm previous data in the literature by demonstrating that immunization in the Nord-Pas-de-Calais area has dramatically decreased the incidence of invasive Hib infections.
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OBJECTIVE: To evaluate a recently developed and manufactured device for monitoring respiratory parameters in mechanically ventilated children. DESIGN: In vitro study using a lung model. SETTING: University paediatric intensive care unit. MATERIAL AND INTERVENTIONS: Evaluation of the accuracy of volume and pressure measurements, of the determination of respiratory system compliance (10 to 30 ml/cmH2O) and of resistance (20 and 50 cmH2O/l per s) by the inflation technique (volume- and pressure-controlled mode of ventilation); assessment of interobserver agreement for compliance (10, 15 ml/cmH2O) and resistance (20, 50 cmH2O/l per s) determinations (ANOVA, intraclass correlation coefficient). MEASUREMENTS AND RESULTS: The accuracy of volume measurements (No.1 Fleisch pneumotachograph) was < or = 5 % of true volumes up to 11 (Flow: 30 l/min) even after the introduction of an endotracheal tube. The accuracy of pressure measurements up to 70 cmH2O was < or = 2.5% of the true values. Coefficients of variation of volume and pressure measurements were < 2%. The accuracy of compliance and resistance determinations was, respectively, < or = 17 and 25% of the true values. No significant observer effect was found on compliance and resistance determinations. Indeed, mean differences in compliance and resistance determinations by pairs of observers were < 1%. Intraclass correlation coefficients were > 0.98. CONCLUSIONS: The measuring error of volume, pressure, compliance and resistance determined using this monitoring system seems acceptable for monitoring purpose. Moreover, use of this system by members of the medical team can be recommended since results obtained by observers, even untrained ones, were similar. In vivo evaluation is now needed.
UNLABELLED: Type 1 allergy against natural rubber latex is an increasing problem in health care workers and children with spina bifida or urogenital malformations. The aim of our study was to evaluate the prevalence of latex IgE antibodies and cross-reacting fruit antibodies in patients with spina bifida compared with atopic and non-atopic controls. Risk factors for sensitization should be determined. Sera of 148 patients with spina bifida and 98 controls (44 with atopy) were screened for IgE antibodies against latex, banana and kiwi by fluorescence enzyme immunoassay (CAP system). Atopies, allergic symptoms after latex contacts and the number of operations were compiled by a questionnaire. Patients with spina bifida developed latex IgE antibodies (> or =0.7 kU/l) more frequently (40.5%) than atopic children (11.4%) or healthy controls (1.9%). All 18 symptomatic patients belonged to the spina bifida group and had high values of latex antibodies. The risk for developing latex antibodies increases with the number of operations. There was no difference in the history of atopic diseases and in a screening test of IgE antibodies against inhalative allergens between latex sensitized and not sensitized children with spina bifida. Antibodies against banana were more frequent in the latex sensitized children with spina bifida. (18.3% vs 3.4%, P = 0.002). CONCLUSION: The high prevalence of latex antibodies in children with spina bifida justifies a primary prophylaxis by avoiding latex contacts, especially during anaesthesia and surgery, a correlation between the number of operations and the development of latex antibodies exists.
BACKGROUND: Recent studies demonstrated that allergy to natural rubber latex is frequently associated with hypersensitivity to avocado fruit. The responsible cross-sensitizing allergen has not been identified. OBJECTIVE: The purpose of this study was to investigate the cross-reactivity of a latex major allergen, hevein, with avocado proteins. METHODS: Serum samples from 118 health care workers (HCWs) allergic to latex (HCW group) and 78 patients with spina bifida (SB) allergic to latex (SB group) were included in this study. Anti-hevein and anti-avocado IgE antibodies were measured by enzyme-linked allergosorbent assay. Cross-reactivity of hevein to avocado proteins was assessed by inhibition of the IgE binding in individual patients' sera containing IgE antibodies to both hevein and avocado. RESULTS: The prevalence of seropositive IgE antibodies to avocado was found to be strongly associated with the presence of hevein-specific IgE antibodies in subjects of both groups (P < .001). Sixty-seven of 91 (73%) subjects from the HCW group and all 19 subjects in the SB group with positive IgE antibodies to hevein also had elevated IgE values to avocado. Competitive RAST inhibition with 42 sera showed that IgE binding to avocado could be completely inhibited in 27 (64%) sera by preincubation with hevein. By contrast, the degrees of inhibition of IgE to hevein by avocado extract ranged from 0% to 36% (n = 16). These results indicate that sensitization to avocado in most patients allergic to latex is caused exclusively by IgE-binding epitopes present in hevein. Results of immunoblots and immunoblot inhibition with 11 serum samples confirmed that a 30-kd protein in avocado was the major IgE-binding component; the IgE-binding reactivity to this protein could be inhibited by hevein in all sera tested. CONCLUSION: Hevein is the major cross-reacting allergen with avocado in subjects with latex allergy.
Rhabdomyolysis results from muscular fibre lysis with release of cellular contents (myoglobin, enzymes, electrolytes) into the plasma. Traumatic (crush syndrome) and non-traumatic rhabdomyolysis have been mostly reported in adults. Traumatic rhabdomyolysis are mostly due to ischemic and reperfusion injuries. Non-traumatic rhabdomyolysis include several factors: muscular compression (comas), cytotoxic injury (infections and poisonings), ischemia (shock, cardiorespiratory arrest) or excessive muscular activity (seizures, strenuous exercise). The main etiologies reported in children are: anoxic-ischemic encephalopathy (including sudden infant death and life threatening events); electrolyte disorders; severe hyperthermia; poisonings; hereditary myopathies. Non-traumatic rhabdomyolysis must be suspected in these circumstances, requiring blood creatinine phosphokinase measurements. Indeed, clinical signs are inconstant and non-specific, and functional signs are difficult to appreciate in children. During the initial phase, the main risk is arrhythmias secondary to hyperkalemia. The two main complications are the compartmental syndrome leading to irreversible vasculo-nervous injuries and acute renal failure. Treatment of traumatic and non-traumatic rhabdomyolysis includes correction of hyperkalemia, active fluid loading in order to prevent acute renal failure and alkalinisation. Prognosis of rhabdomyolysis relates to the aetiology and the presence of acute renal failure.
BACKGROUND AND OBJECTIVE: Spina bifida patients are at a high risk of developing latex allergy. Recently, we found a relationship between the IgE responsiveness to latex allergen hevein and human leucocyte antigen (HLA) alleles DRB1*04(DR4) as well as DQB1*0302(DQ8). This study was carried out to investigate the association between HLA class II alleles and the specific IgE response to latex allergen Hev b 1 in spina bifida patients. METHODS: Blood samples from 103 unrelated German spina bifida patients exposed to latex products and from 90 unsensitized controls were examined. Genomic DNA isolation followed by HLA-D-specifc polymerase chain reaction (PCR) amplification was used to perform HLA typing of allelic polymorphisms in exon 2 of DQB1 and of DRB1,3,4,5 with sequence-specific oligonucleotide probes (SSOPs). RESULTS: Fifty-one out of 103 spina bifida patients were found to have anti-latex IgE antibodies; 40 had also anti-Hev b 1 antibodies. Further, we observed that 80% of the Hev b 1 responders underwent five or more surgeries whereas 55% of the Hev b 1 non-responders and 75% of the latex-non-responders underwent less than five surgical interventions. From the latex-sensitized group 33% showed an elevated phenotype frequency of DRB1*0701(DR7) when compared with unsensitized patients (12%, P = 0.0095, Pc = NS) and with controls (17%; P = 0.035, Pc = ns). Fifteen out of 40 Hev b 1 responders also exhibited an elevated DR7 frequency when compared with latex-sensitive but Hev b 1-negative patients (38% vs 18%, P = NS) or with unsensitized controls (38% vs 17%, P = 0.013, Pc = NS). CONCLUSIONS: Although we found that the DRB1*0701 (DR7) phenotype frequency was elevated in SB patients with latex- as well as with Hev b 1-IgE responsiveness, the analyses of the other class II alleles clearly demonstrate that the HLA-D region does not play a major role in the pathogenetic way of sensitization to Hev b 1.
BACKGROUND: The effect of latex prophylaxis has not been investigated in spina bifida children, a high-risk group for latex allergy. As repeated operations have been identified as a major cause of latex sensitization, we wanted to find out whether primary latex prophylaxis during surgery could prevent latex allergy in children with spina bifida. METHODS: In December 1995, we established latex-free surgery and anesthesia for all patients with spina bifida regardless of their sensitization to latex. Twelve children born after that date (mean age 1.2 years, mean number of operations 3.3, range 1-7) were tested for specific IgE against latex until December 1997 (ImmunoCap, Pharmacia, Uppsala, Sweden) and compared with eight children born before December 1995 (mean age 1.3 years, mean number of operations 3.6, range 1-8), in whom a test for latex IgE had been done before the age of 2 years. RESULTS: Before we established primary prophylaxis, three of seven children with spina bifida (38%) were sensitized to latex until the age of 2 years. After the establishment of a latex-free operating theater for spina bifida patients, none of the 12 patients were sensitized to latex despite up to seven operations in each child. CONCLUSIONS: Primary latex prophylaxis during surgery can prevent latex sensitization in young spina bifida patients.
The course of latex sensitization is rarely documented, and only a few reports about the influence of prophylaxis in the occupational environment have been published concerning health care workers. Therefore we did a follow-up study in the high risk group of patients with spina bifida and evaluated the efficacy of latex prophylaxis. For this purpose we measured IgE antibodies (FEIA) against latex and inhalative allergens in the sera of 67 patients with spina bifida and reevaluated them 0.6 to 4.1 years later, having instructed the patients about prophylactic measures and established a latex-free environment for surgery of all spina bifida patients in our hospital. 37% of the patients did not develop latex antibodies during the follow-up period, 27% showed decreasing levels of antibodies (12% to non-detectable levels), 19% had an increase in latex sensitization (6% newly sensitized), and 9% showed no change in levels of latex antibodies. From our data it may be concluded that surgery without strict latex prophylaxis is the main cause of new sensitization and worsening of preexisting latex antibody levels. Mild sensitization can be reduced by prophylactic measurements to non-detectable antibody levels. With consistent prophylaxis, even symptomatic patients can be operated without risk of allergic complications or increasing antibodies.
A PCR assay for detection of enterovirus RNA in multiple specimen types from patients with neurological infections was evaluated. Combined PCR assay of cerebrospinal fluid and serum (systemic specimens) was more sensitive than assaying either specimen alone in children but not in adults. Compared with PCR in systemic specimens, detection of enterovirus RNA in throat swabs showed a sensitivity of 62.5% and a specificity of 75.6%.